Multimodal circulating tumor DNA (ctDNA) colorectal neoplasia detection assay for asymptomatic and early-stage colorectal cancer (CRC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3536-3536
Author(s):  
Jeeyun Lee ◽  
Hee C Kim ◽  
Seung Tae Kim ◽  
Yupeng He ◽  
Paul Sample ◽  
...  
Keyword(s):  
Early Stage ◽  
Colorectal Neoplasia ◽  
High Sensitivity ◽  
High Specificity ◽  
Stage I ◽  
Stage Iii ◽  
Average Risk ◽  
Crc Screening ◽  
Large Patient ◽  
Detection Assay

3536 Background: To improve average risk CRC screening compliance, additional options are needed, especially options that address patient and provider reported barriers such as time and convenience. LUNAR-2 is a multimodal blood-based colorectal neoplasia detection assay incorporating ctDNA assessment of somatic mutations and tumor derived methylation and fragmentomic patterns, aimed to maximize sensitivity for early stage CRC detection. We evaluated this test in a large patient cohort with newly diagnosed CRC. Methods: Individuals diagnosed with CRC between 2013-2016 consented to provide blood samples prior to surgical resection. Those treated with neoadjuvant chemotherapy were excluded. Isolated plasma samples (median 3mL from EDTA) from 434 individuals were analyzed with LUNAR-2 (Guardant Health, USA) and included in the analysis. Median age at CRC diagnosis was 63 years (range 28 - 89) and 41% were female. Control samples were from 271 age-matched cancer free individuals. “ctDNA detected” and “ctDNA not detected” results were generated by a model trained on a separate sample set (N=614) from both cancer free individuals and those with CRC. Calling threshold was determined based on this held-out set to target 90% specificity. ctDNA results and clinical characteristics were correlated. Results: Overall CRC sensitivity was 91% (393/434), with high sensitivity across all stages; 88% Stage I/II, 93% Stage III (Table). Specificity was 94% (255/271). There was no difference in sensitivity when excluding those with early (<45 years) or late (>84 years) onset CRC (90% sensitivity; 388/429; p=0.95; 88% Stage I/II, 93% Stage III). There were no differences in sensitivity for asymptomatic CRC (88%) compared to symptomatic CRC (91%; p=0.4; Table). However, higher cell-free DNA tumor fractions were observed in the symptomatic cohort. Sensitivity for detection of right-sided and left-sided CRC was similar (93% vs. 90%; p=0.5; Table). Conclusions: In this large early-stage CRC cohort, multimodal ctDNA assessment has high sensitivity for CRC detection with high specificity. Equivalent sensitivity in the asymptomatic cohort suggests this test will have clinically meaningful performance in an average risk screening population. A prospective registrational study is ongoing to evaluate the test in an average risk CRC screening cohort.[Table: see text]

Accurate early-stage colorectal cancer detection through analysis of cell-free circulating tumor DNA (ctDNA) methylation patterns.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3606-3606
Author(s):  
James M. Kinross ◽  
Pol Canal-Noguer ◽  
Marko Chersicola ◽  
Primož Knap ◽  
Marko Bitenc ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Machine Learning ◽  
Cancer Detection ◽  
Learning Algorithm ◽  
Early Stage ◽  
Country Of Origin ◽  
Stage I ◽  
Stage Iii ◽  
Machine Learning Algorithm ◽  
Crc Screening

3606 Background: Colorectal cancer (CRC) screening programs suffer from poor uptake and biomarkers have limited diagnostic accuracy. The measurement of the methylation status of tumor-derived cell-free DNA in plasma may address these challenges. We used a targeted methylation panel, tumor-derived signal deduction and machine learning algorithm to refine a blood test for the detection of early-stage CRC. Methods: This was a prospective, international multicenter observational cohort study. Plasma samples were collected either prior to a scheduled colonoscopy as part of standard colorectal cancer screening or prior to colonic surgery for primary CRC. Differentially methylated regions (DMRs) were initially selected by analyzing CRC and control tissue samples with whole genome bisulfite sequencing. A targeted sequencing assay was designed to capture these DMRs in plasma ctDNA. Individual sequencing reads were evaluated for cancer-specific methylation signal and scores calculated for each DMR in a sample. A panel of methylation scores originating from 203 DMRs was used in a prediction model building and validated in a test cohort of patients. Results: Calculated scores were used to train a machine learning model on 68 ctDNA samples from 18 early stage (I-II) and 16 late-stage (III-IV) CRC patients and 34 age, BMI, gender and country of origin matched neoplasia-free controls (median age 63 [50-74], mean BMI 27 [19.5-37], female 50%, Spanish and Ukrainian population, distal cancers 50%). This model was then applied to an independent set of subjects from Spanish, Ukraine and Germany, including 36 stage I-IV cancer patients (median age 61.5 [55-82], BMI 28 [16-39], female 47%, 42% of the tumors were distal) and 159 age and sex matched controls. 87 of the control patients had a negative colonoscopy finding (cNEG), 19 had hyperplastic polyps (HP), 37 had small non-advanced adenomas (NAA) and 16 were diagnosed with other benign gastrointestinal diseases (GID). The model correctly classified 92% (33/36) of CRC patients. Sensitivity per cancer stage ranged from 83% (5/6) for stage I, 92% (11/12) for stage II, 92% (12/13) for stage III to 100% (5/5) for stage IV. Specificity of the model was 97% (154/159), with 100% (37/37) NAA, 94% (15/16) GID, 95% (18/19) HP and 97% cNEG patients correctly identified. Lesion location, gender, BMI, age and country of origin were not significantly correlated to prediction outcome. Conclusions: Methylation sequencing data analyzed using read-wise scoring approach combined with a machine-learning algorithm is highly diagnostic for early-stage (I-II) CRCs (89% sensitivity at 97% specificity). This method could serve as the basis for a highly accurate and minimally invasive blood-based CRC screening test with significant implications for the clinical utility of ctDNA in early-stage cancer detection.

scholarly journals International Study of Primary Mucinous Ovarian Carcinomas Managed at Tertiary Medical Centers

2018 ◽  
Vol 28 (5) ◽  
pp. 915-924 ◽  
Author(s):  
Jennifer J. Mueller ◽  
Henrik Lajer ◽  
Berit Jul Mosgaard ◽  
Slim Bach Hamba ◽  
Philippe Morice ◽  
...  
Keyword(s):  
Early Stage ◽  
Statistical Tests ◽  
Stage Iv ◽  
Stage I ◽  
Stage Iii ◽  
Oncologic Outcomes ◽  
Disease Stage ◽  
Ovarian Carcinomas ◽  
Early Stage Disease ◽  
Medical Centers

ObjectiveWe sought to describe a large, international cohort of patients diagnosed with primary mucinous ovarian carcinoma (PMOC) across 3 tertiary medical centers to evaluate differences in patient characteristics, surgical/adjuvant treatment strategies, and oncologic outcomes.MethodsThis was a retrospective review spanning 1976–2014. All tumors were centrally reviewed by an expert gynecologic pathologist. Each center used a combination of clinical and histologic criteria to confirm a PMOC diagnosis. Data were abstracted from medical records, and a deidentified dataset was compiled and processed at a single institution. Appropriate statistical tests were performed.ResultsTwo hundred twenty-two patients with PMOC were identified; all had undergone primary surgery. Disease stage distribution was as follows: stage I, 163 patients (74%); stage II, 8 (4%); stage III, 40 (18%); and stage IV, 10 (5%). Ninety-nine (45%) of 219 patients underwent lymphadenectomy; 41 (19%) of 215 underwent fertility-preserving surgery. Of the 145 patients (65%) with available treatment data, 68 (47%) had received chemotherapy—55 (81%) a gynecologic regimen and 13 (19%) a gastrointestinal regimen. The 5-year progression-free survival (PFS) rates were 80% (95% confidence interval [CI], 73%–85%) for patients with stage I to II disease and 17% (95% CI, 8%–29%) for those with stage III to IV disease. The 5-year PFS rate was 73% (95% CI, 50%–86%) for patients who underwent fertility-preserving surgery.ConclusionsMost patients (74%) presented with stage I disease. Nearly 50% were treated with adjuvant chemotherapy using various regimens across institutions. The PFS outcomes were favorable for those with early-stage disease and lower but acceptable for those who underwent fertility preservation.

Patterns of lung cancer in people living with human immunodeficiency virus (HIV): A retrospective, single-center study in Washington, D.C.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21154-e21154
Author(s):  
Margaret Pruitt ◽  
Rajesh Naidu Janapala ◽  
Faysal Haroun
Keyword(s):  
Lung Cancer ◽  
Late Stage ◽  
Early Stage ◽  
Primary Lung Cancer ◽  
Large Cell ◽  
Molecular Data ◽  
Stage I ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Neuroendocrine Cancer

e21154 Background: Lung cancer is the leading cause of cancer death and the most common non-acquired immune deficiency syndrome defining malignancy in people living with HIV (PLWH). Disparities in outcomes have been observed despite lung cancer mortality reportedly decreasing in the general population over the last decade due to lower rates of smoking and the advent of novel therapies. To better understand the current trend in lung cancer in PLWH, we explored demographic characteristics, comorbidities, and lung cancer pathology and molecular data in this population. Methods: A retrospective search of patient charts was conducted from 2004 to January 2021 using billing codes for HIV and primary lung cancer. Patients who had incorrect HIV or primary lung cancer diagnoses were excluded. Results: The search yielded 45 patients, of which 11 were excluded as described above: 66% were males, 82% African American, and 18% Caucasian. About two-thirds of patients were living in zip codes with predominantly low to medium household incomes. The median pack years of patients diagnosed with Stage I or II non-small cell lung cancer (NSCLC) was 40, Stage III or IV NSCLC was 20, early stage small cell lung cancer (SCLC) was 30, and late stage SCLC was 60. The median time between HIV and lung cancer diagnoses was 21.7 years for Stage I or II NSCLC, 17.1 years for Stage III or IV NSCLC, 15.2 for early stage SCLC, and 13.3 for late stage SCLC. Of 26 patients with viral load (VL) data, 21 (80.7%) had VL less than 500 when lung cancer was diagnosed. Of the 33 charts with available pathology data, there were 16 adenocarcinomas, 6 squamous carcinomas, 3 adenosquamous carcinomas, 1 large cell neuroendocrine cancer, 4 SCLCs, 1 mesothelioma, and 2 unspecified NSCLCs. Of 19 patients with a histologic grade, 11 had a high-grade tumor (57.9%). For the NSCLCs, 8 were Stage I (28.5%), 2 Stage II (7.1%), 8 Stage III (28.5%), 9 Stage IV (32.1%), and 1 with an unspecified stage. One SCLC was early stage and the remaining 3 were late stage. Five patients had brain metastasis. Molecular data or PDL-1 expression was available for 10 adenocarcinomas (62.5%), 1 adenosquamous (33%), 3 squamous carcinomas (50%), and the large cell neuroendocrine cancer. An EGFR mutation was detected in 2 cancers. ALK rearrangement was found in 1. Other mutations were detected. Two cancers were in each PDL1 expression category: < 1%, 1-50%, and > 50%. Conclusions: Our study suggests that PLWH with lung cancer continue to have high rates of smoking. Viral load was well controlled. A range in stages of lung cancer was observed including earlier stages. Although molecular data was limited, available EGFR and ALK gene alterations, and PD-L1 expression prevalence were on par with that of the general population. With advancements in lung cancer treatment, additional research is needed in the PLWH population to better understand and mitigate disparities.

Development of recombinase polymerase amplification combined with lateral flow detection assay for rapid and visual detection of Ralstonia solanacearum in tobacco

Plant Disease ◽  
2021 ◽  
Author(s):  
Changfeng Li ◽  
Yuliang Ju ◽  
Xun Wu ◽  
Pengfei Shen ◽  
Le Cao ◽  
...  
Keyword(s):  
Ralstonia Solanacearum ◽  
Visual Detection ◽  
High Sensitivity ◽  
High Specificity ◽  
Lateral Flow ◽  
Recombinase Polymerase Amplification ◽  
Molecular Diagnostic ◽  
Tobacco Stem ◽  
Detection Assay ◽  
Flow Detection

Bacterial wilt caused by Ralstonia solanacearum is a serious soil-borne disease that results in severe losses to tobacco (Nicotiana tabacum) production in China. In this study, a novel RPA-LFD assay for the rapid visual detection of R. solanacearum was established using recombinase polymerase amplification (RPA) and lateral-flow dipstick (LFD). The RPA-LFD assay was performed at 37°C in 30 min without complex equipment. Targeting the sequence of the RipTALI-9 gene, we designed RPA primers (Rs-rpa-F/R) and an LF probe (Rs-LF-probe) that showed high specificity to R. solanacearum. The sensitivity of RPA-LFD assay to R. solanacearum was the same as that in conventional PCR at 1 pg genomic DNA, 102 CFU/g artificially inoculated tobacco stem, and 103 CFU/g artificially inoculated soil. The RPA-LFD assay could also detect R. solanacearum from plant and soil samples collected from naturally infested tobacco fields. These results suggest that the RPA-LFD assay developed in this study is a rapid, accurate molecular diagnostic tool with high sensitivity for the detection of R. solanacearum.

QIM19-124: Does Virtual Navigation Improve Care Continuity and Compliance in Patients With Early Stage Colon Cancer?

2019 ◽  
Vol 17 (3.5) ◽  
pp. QIM19-124
Author(s):  
Dayna Crawford ◽  
Brook Blackmore ◽  
Jeremy Ortega ◽  
Erica Williams
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Stage I ◽  
Stage Iii ◽  
Nccn Guidelines ◽  
Care Continuity ◽  
Colon Cancers ◽  
Follow Up Care

Background: Colon cancer is the 3rd most common cancer in men and women combined, with an occurrence rate of 4.49% for men and 4.15% for women. The 2018 expectation is 50,630 deaths related to colon cancer in the United States (American Cancer Society Facts and Figures 2018). Early detection is increasing with nearly 45% of colon cancers diagnosed as stage I/II (Sarah Cannon Cancer Registry 2015). Treatment for early stage I/II colon cancer patients usually involves surgery then surveillance. On-site navigators perform their duties by patient need and barriers to care. Late stage III/IV colon cancer patients require more assistance and face more barriers, which often leaves early stage I/II patients without an advocate. This disparity can lead to lower rates of follow-up care for early stage I/II patients. Sarah Cannon created a program for virtual colon navigation (VCN) to determine if early stage I/II patients benefit from a virtual navigator who offers support by phone throughout their disease process. Objectives: The goal was to increase early stage I/II patients’ knowledge of their cancer and convey the importance of compliance with follow-up care, such as repeat colonoscopy as recommended by their physician and NCCN Guidelines. Methods: By developing software that utilizes artificial intelligence, Sarah Cannon created an automated process to identify colon cancer patients at the time of diagnosis. This technology then routes positive pathology reports to a VCN who contacts the early stage I/II patients by telephone, ensuring patient connection to the suitable physician for treatment. The VCN helps patients understand their diagnosis, provides education, assesses barriers to care, connects to resources, provides emotional support, and offers assistance with follow-up for physician visits, imaging and procedures such as colonoscopies, based upon NCCN Guidelines and physician guidelines. The VCN also connects stage III/IV patients with an on-site navigator in their region for more hands-on navigation. Results: Through September 2018, Sarah Cannon navigated 734 colon cancers, 332 stage I/II and 402 stage III/IV. With our increased capacity, Sarah Cannon/HCA maintained a 98% rate of follow-up care with new diagnoses of all stages of colon cancer. Conclusions: The VCN program allowed Sarah Cannon/HCA to improve care continuity and compliance based upon NCCN Guidelines for early stage I/II colon cancer patients throughout 5 regions and 37 facilities.

Characteristics and outcomes of extranodal NK/t-cell lymphoma (ENKL): A North American (NA) multi-institutional experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8060-8060
Author(s):  
Lauren Shizue Maeda ◽  
Jessica L. Geiger ◽  
Kerry J. Savage ◽  
Jim Rose ◽  
Lauren C. Pinter-Brown ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Early Stage ◽  
Combined Modality Therapy ◽  
Progression Free Survival ◽  
T Cell Lymphoma ◽  
Stage I ◽  
Stage Iii ◽  
Cell Transplant ◽  
Early Stage Disease

8060 Background: ENKL is a rare and aggressive subtype of peripheral T-cell lymphoma. Due to its geographic predilection there is a paucity of data on clinical experiences from non-Asian countries. The purpose of this study was to analyze characteristics and outcomes of patients (pts) with ENKL identified from major academic centers in NA. Methods: Pts with newly diagnosed CD56+ ENKL were retrospectively identified. Analyses included disease characteristics, ethnicity, therapy, and outcomes. Results: 115 pts (63.5% Caucasian, 20% Asian, 16.5% other) were identified across 10 centers diagnosed between 5/1990-5/2011 (Era 1: pre-2000, n=16; Era 2: 2000-2005, n=45; Era 3: post-2005, n=54). Median age was 52 years (19-88). 75 (65%) had stage I/II disease and were treated with combined modality therapy (CMT) n=48, chemotherapy (CT) n=14 or radiotherapy (RT) n=14. 40 pts had stage III/IV disease and were treated with CT (n=23), CMT (n=12) or RT (n=5). CT regimens used alone or in CMT were either anthracycline-based (n=68) or other (n=29). 63% of stage I/II pts and 40% with stage III/IV achieved complete remission (CR). 30 pts underwent a stem cell transplant (SCT); 14 in first CR and 16 at progression/relapse (autologous, n=21; allogeneic, n=9). Pts with stage I/II disease had a better progression-free survival (PFS) and overall survival (OS) compared with stage III/IV (12 vs 5.2 months (p=0.003) and 41.5 vs 8.9 months (p<0.0001), respectively). For all stages, treatment with CMT compared with CT or RT alone was also associated with better PFS and OS, 18.0 vs 3.9 months (p<0.0001), and 41.5 vs 10.2 months (p=0.002) respectively. Non-anthracycline-based regimens were associated with better PFS (p=0.001) and OS (p=0.045). No survival differences were seen between Asian and non-Asian pts. Conclusions: This series represents one of the largest experiences of ENKL in NA. Our data are consistent with Asian studies in: 1) majority of pts present with early stage disease; 2) overall poor outcome; 3) superiority of CMT and non-anthracycline regimens. Advances in understanding biology and international collaborative efforts are required to improve outcome in this rare entity.

Adult granulosa cell tumors (GCT): 56 years of clinicopathologic outcomes including FOXL2 mutational status.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5536-5536
Author(s):  
Michelle Wilson ◽  
Roseanne Rosario ◽  
Kathryn F. Chrystal ◽  
Kathryn Payne ◽  
Barrie David Evans ◽  
...  
Keyword(s):  
Hormonal Therapy ◽  
Survival Data ◽  
Early Stage ◽  
Stage I ◽  
Stage Iii ◽  
Disease Stage ◽  
Late Relapse ◽  
Mutation Status ◽  
Mutational Status ◽  
Risk Of Relapse

5536 Background: GCT account for 2-3% of ovarian cancers with a tendency for late relapse. Treatment is primarily surgical. The role of chemotherapy and hormonal therapy is more controversial. The FOXL2 mutation (402C→G) has been identified as a potential driver mutation and may be useful in diagnosis and treatment. Methods: We performed a retrospective review of GCT patients (pts) referred to the Auckland Gynae-Oncology Multidisciplinary Team from 1955 to 2011. Baseline characteristics, clinical course, histopathology and survival data was recorded. FOXL2 mutation status was determined by DNA sequencing, and correlated with clinical data. Results: 56 GCT pts were identified. Median (med) age 48.6 years (y) (22-86). Stage I were 82.1%. 48% of tumours were ≥10cm. Med follow up was 10.0y (0.2-40.4). 25 pts progressed, med time to progression (TTP) was 4.5y (0.1-17.7). Med progression free survival was 14.5y. Med overall survival (OS) was 21.8y but med disease specific survival was not reached. 9/18 pts died of disease. Stage III GCT and size ≥10cm had a higher risk of relapse (RR 3.1 and 2.9) and death (RR 8.2 and 8.6) respectively. 17/46 (37%) Stage I pts progressed. Med TTP was 8.3y (1.3 to 17.7), med OS was 29.0y. Stage I relapse rate was higher in tumours ≥10cm (RR 3.9 p<0.01). 12/17 1st relapses were treated with surgery. 10/17 pts received ≥1 line of chemotherapy and 7 ≥1 hormonal therapy. Clinical benefit rates (CR, PR and SD>6m) for first-line chemotherapy was 25% and 71% for hormones. All 7 Stage III pts progressed with med OS of 6.3yr (0.2-12.3y). Currently the FOXL2 mutation statuses are known for 18 patients. 89% carried the mutation. Homozygous, heterozygous and wild-type mutations had no difference in risk of relapse or death. Further FOXL2 mutation analysis is ongoing. Conclusions: This long term series confirms the protracted natural history of this disease. Early stage GCT, despite progression has a good prognosis with med OS >25y. Stage and tumour size remain the most consistent prognostic factors. Whilst surgery remains the mainstay of therapy, the high response rate to hormonal therapy deserves investigation. Currently the FOXL2 mutation status does not appear prognostic but this needs further research.

Serum Thymidine Kinase and Beta-2 Microglobulin in Monoclonal Gammopathies

1987 ◽  
Vol 73 (5) ◽  
pp. 445-449 ◽  
Author(s):  
Giovanni Ucci ◽  
Alberto Riccardi ◽  
Renata Luoni ◽  
Paolo Spriano ◽  
Giampaolo Merlini ◽  
...  
Keyword(s):  
Thymidine Kinase ◽  
Early Stage ◽  
Sharp Decrease ◽  
Fold Increase ◽  
Stage I ◽  
Stage Iii ◽  
Clinical Value ◽  
Monoclonal Gammopathies ◽  
Low Levels ◽  
Beta 2 Microglobulin

We evaluated the serum thymidine kinase (TK) and β-2 microglobulin (β-2) levels of 22 patients with monoclonal gammopathy of undetermined significance (MGUS) and of 29 patients with multiple myeloma (MM). Both parameters were significantly lower in MGUS than in MM patients and in early (stage I+II) than in advanced (stage III) MM. TK was also lower in MGUS than in stage I MM (p < 0.025). A seven-fold increase of TK level was documented in one patient who developed a full blown picture of MM 6 years after a diagnosis of MGUS. In 3 patients with stage III MM, a sharp decrease in TK (40–77%) and in β-2 (29–53%) levels at remission was evident with respect to the levels measured at diagnosis. Patients with high levels of TK or [3-2 had a shorter survival than those with low levels; however, this was statistically significant only for β-2 levels (p < 0.02). Serum TK as well as β-2 levels appear to be of clinical value in monoclonal gammopathies and related to the course of the disease.

scholarly journals Analysis of A 6-Mirna Signature in Serum from Colorectal Cancer Screening Participants as Non-Invasive Biomarkers for Advanced Adenoma and Colorectal Cancer Detection

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1542 ◽  
Author(s):  
María Marcuello ◽  
Saray Duran-Sanchon ◽  
Lorena Moreno ◽  
Juan José Lozano ◽  
Luis Bujanda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Detection ◽  
Diagnostic Performance ◽  
Colorectal Neoplasia ◽  
Precancerous Lesion ◽  
Advanced Adenoma ◽  
Average Risk ◽  
Mirna Signature ◽  
Crc Screening ◽  
Non Invasive

Early detection of colorectal cancer (CRC) and its precancerous lesion, advanced adenomas (AA), is critical to improve CRC incidence and prognosis. Circulating microRNAs (miRNAs or miR) are promising non-invasive biomarkers for cancer detection. Our previous results showed that a plasma 6-miRNA signature (miR-15b-5p, miR-18a-5p, miR-29a-3p, miR-335-5p, miR-19a-3p and miR-19b-3p) could distinguish between CRC or AA and healthy individuals (controls). However, its diagnostic performance in serum is unknown. In this exploratory study we aim to evaluate the diagnostic performance of the 6-miRNA signature in serum samples in a cohort of individuals participating in Barcelona’s CRC Screening Programme. We prospectively collected serums from 264 faecal immunochemical test (FIT)-positive participants and total RNA was extracted. Finally, 213 individuals (CRC, 59, AA, 74, controls, 80) were included. MiRNA expression was quantified by real-time RT-qPCR and data analysis was performed by logistic regression. Faecal hemoglobin concentration (f(Hb)) from FIT of the same individuals was also considered. As previously described in plasma, serum from patients with AA or CRC presented significant differences in the 6-miRNA signature compared to controls. Moreover, when combined with f(Hb), the final signature showed high discriminative capacity to distinguish CRC from controls (area under the curve (AUC) = 0.88), and even AA (AUC = 0.81) that otherwise are poorly detected if we only consider f(Hb) (AUC = 0.64). Addition of the serum 6-miRNA signature to quantitative f(Hb) show high accuracy to detect patients with advanced colorectal neoplasia in average-risk individuals. A combination of these two non-invasive methods could be a good strategy to improve diagnostic performances of current CRC screening programmes.

Sensitivity of second-generation blood-based methylated Septin9 assay for early-stage colorectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 419-419 ◽  
Author(s):  
Gunter Weiss ◽  
Anne Fassbender ◽  
Thomas Koenig ◽  
Reimo Tetzner
Keyword(s):  
Colorectal Cancer ◽  
Real Time ◽  
Real Time Pcr ◽  
Early Stage ◽  
Screening Colonoscopy ◽  
Molecular Diagnostic ◽  
Control Group ◽  
Average Risk ◽  
Early Stage Disease ◽  
Crc Screening

419 Background: Early detection of colorectal cancer (CRC) has been shown to decrease mortality, although compliance to CRC screening is low. Availability of a blood-based test is expected to improve CRC screening compliance. Specific detection of CRC using the Septin9 biomarker (mSEPT9) in a large prospective trial of an average-risk CRC screening population exhibited 67% sensitivity for CRC with 88% specificity. Laboratory-developed tests detecting mSEPT9 in plasma are now available in North America and a 2nd generation molecular diagnostic blood test for mSEPT9 is available as a CE-marked kit in Europe. The current research evaluated the clinical performance of the 2nd generation mSEPT9 assay. Methods: Bisulfite-converted DNA (bisDNA) was prepared from 3.5 mL human plasma using the 2ndgeneration plasma DNA preparation kit. Resulting bisDNA was analyzed in triplicate on the ABI7500 Fast Dx (Life Technologies, Inc.) using proprietary HeavyMethyl real-time PCR technology for mSEPT9 and the 2nd generation real-time PCR kit. In a case – control design, plasma from 98 CRC patients (n = 87 stages I - III) and 99 age-matched, colonoscopy-verified normal individuals were processed with the mSEPT9 assay. In addition, plasma from 150 prospectively enrolled average risk individuals scheduled for screening colonoscopy was tested. mSEPT9 was qualitatively analyzed such that any detection of mSEPT9 in a PCR was called “positive”. Results: The revised mSEPT9 assay exhibited 95% sensitivity (95% CI: 89-98%) for CRC. Sensitivity for stage I was 89% (95% CI: 72-96%, n = 27) and sensitivity for stage II was 93% (95% CI: 78-98%, n = 29). The control group was positive at a rate of 16% (95% CI: 10-25%). Specificity of the mSEPT9 assay in the screening cohort was 85% (95% CI: 78-89%). Conclusions: The 2nd generation mSEPT9 assay demonstrated improved sensitivity for CRC without significant impact on specificity. The enhanced design and robustness of the assay will further facilitate its standardized use in routine laboratory settings. Finally, the increased sensitivity of the revised mSEPT9 assay improves the detection of early stage disease and demonstrates the feasibility of a blood-based CRC screening technology.

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