Concordance Study Research Articles

P89.06 Prospective Concordance Study of a Multi-Gene PCR Assay and NGS for the Detection of Targetable Gene Alterations in Lung Cancer

P89.06 Prospective Concordance Study of a Multi-Gene PCR Assay and NGS for the Detection of Targetable Gene Alterations in Lung Cancer

Concordance and characterization of massively parallel sequencing at 58 STRs in a Tibetan population.

BackgroundMassively parallel sequencing (MPS) is a promising supplementary method for forensic casework in short tandem repeats (STRs) genotyping, owing to several advantageous features in comparison to traditional capillary electrophoresis (CE). However, the application of MPS in casework requires accessible datasets from the worldwide population to enrich the allele frequencies of sequence‐based STR genotypes.MethodsIn this study, we report the characterization of sequence‐based allele frequencies of 58 STRs from a Tibetan population comprising 120 unrelated individuals using the ForenSeq™ DNA Signature Prep Kit. A concordance study evaluating MPS and CE allele data was performed to ensure that MPS is compatible with current CE‐based forensic databases. The diversity of observed alleles, allele frequencies, and forensic parameters per locus by length (LB), sequence without flanking region (RSB), and sequence with flanking region (FSB) were analyzed and compared.ResultsThe concordance study demonstrated a concordance rate exceeding 99%. The combined random match probability (RMP) for the 26 A‐STRs was 2.04 × 10–29, 1.93 × 10–31, and 9.56 × 10–33 for LB, RSB, and FSB, respectively. Similar trends were observed in other forensic parameters resulting from the increase in the number of unique alleles available. A total of 111 and 113 unique haplotypes in the Y‐STR loci were observed when using length‐based and sequence‐based alleles, respectively. In addition, we identified 35 novel alleles at 25 loci and 25 polymorphisms in the flanking regions at 17 STRs.ConclusionsOur data suggest that MPS‐ and CE‐derived alleles are compatible. MPS‐based analysis of the STR data substantially increased the allele diversity and improved the forensic parameters, which clearly demonstrated the advantages of MPS in comparison to CE. With more pooled data and larger‐scale validation, MPS could play a valuable role in forensic genetics and might be an additional tool for routine casework.

A concordance study determining language dominance between navigated transcranial magnetic stimulation and the Wada test in patients with drug-resistant epilepsy

ObjectiveIt remains unclear whether transcranial magnetic stimulation (TMS) can replace the Wada test to determine language hemisphere dominance (HD). Using the Wada test as the gold standard, this study aimed to investigate the accuracy of navigated TMS (nTMS) in determining language HD. MethodsThis study enrolled nine right-handed patients with drug-resistant epilepsy. We hypothesized that application of nTMS to language-related areas of the language-dominant hemisphere would induce positive manifestation of language dysfunction (LD). To test our hypothesis, the patients were instructed to perform a visual object-naming task while nTMS was applied to the anterior (e.g., Broca’s area) and posterior (e.g., Wernicke’s area) regions, which are closely related to language processing. The Wada test result was used as the gold standard, and the diagnostic value of nTMS was assessed using the Kappa consistency test. ResultsThe nTMS-induced LD positive rate for the bilateral anterior language areas (85.7%) was higher than that for the posterior language areas (57.1%). There was high consistency between nTMS stimulation of the left anterior and posterior language areas and the Wada test results for determining language HD. In contrast, the consistency of stimulation of the right anterior and posterior transfer sites was moderate (Kappa value = 0.545, P = 0.171) and low, respectively. For the latter, no statistical calculation was performed because stimulation of the right posterior speech area was negative in all patients compared with the Wada test results. ConclusionsOur findings revealed that using nTMS to stimulate language-related left anterior and posterior areas could predict language HD with high accuracy. When the stimulation performance of these areas is positive, nTMS and the Wada test are equally accurate. Observing only negative performance may indicate that language HD has been transferred to the right side.

Abstract PS8-22: Augmentation of a minimal multidisciplinary tumor board with clinical decision support to triage breast cancer patients in the UK

Abstract BackgroundAll UK cancer patients undergo required assessments by a full Multidisciplinary Tumor Board (fMTB) at key treatment decision points, placing a resource burden on the healthcare system. Watson for Oncology (WfO) is a decision-support system that presents therapeutic options to cancer-treating clinicians. This study is an initial phase of an evaluation at Guys and St. Thomas’ NHS Hospital (GSTT), designed to explore the extent to which WfO can be used by the fMTB to triage less complex patient cases and ultimately reduce workload and time pressures currently experienced by fMTBs. We conducted a concordance study with two minimal MTB teams (mMTB) for Stage I-III breast cancer patients. MethodsBreast cancer cases (N=63) treated from 2017-2018 at GSTT were evaluated by 2 independent mMTBs, blinded to each other and previous fMTB decisions rendered prior to this study. Each mMTB consisted of a senior medical oncologist and surgeon; GSTT’s 12+ member fMTB is comprised of oncologists, surgeons, radiologists, pathologists and others. mMTBs were shown options that were either listed as ‘recommended’ or ‘for consideration’ by WfO and given the opportunity to revise prior decisions. The combined 4-person minimal MTB (cmMTB) consisting of both 2-person mMTBs provided a current consensus best-practice plan and systemic therapy recommendations for discordant cases. We evaluated the concordance of WfO’s systemic therapeutic recommendations and mMTBs, as well as concordance with the cmMTB. Previous decisions by the fMDTB were also compared to decisions by the cmMTB. Univariate logistic regression explored characteristics predictive of concordance with the cmMTB. ResultsFor treatment plans, WFO’s therapeutic options had higher concordance with cmMTB decisions than either mMTB alone (concordance 93.7% vs. 92.1%) or the previous decisions by the fMTB (87.3). For systemic therapy decisions, the WfO-cmMDTB concordance was 70.2%; however, adjusting for non-NICE approved drugs and the common practice of Carboplatin use in the UK, concordance increased to 91.5%. Previous decisions by the fMTB had the lowest concordance with the cmMTB (87.3%). Adjusting for the UK-practice related use of Carboplatin, WfO had slightly higher concordance with cmMTB systemic therapy decisions than either mMTB alone (89.4% and 87.2%). Univariate analysis with this limited sample revealed non-significant trends in association between mMTB’s concordance with WfO and stage of cN at diagnosis, HER2 status, tumor location and grade. For example, mMTBs concordance with WfO tended to improve when tumor grade was high. Non-significant trends were also identified in the association between WfO-treatment concordance and tumor location, where treatment concordance increased with medial tumor location. ConclusionIn this small cohort study, a clinical decision-support tool demonstrated better agreement with UK best practice treatment than a 2-person mMTB and may have a role in triaging breast cancer cases in the UK. Citation Format: Hartmut Kristeleit, Martha Martin, Christina Karampera, Rezzan Hekmat, Bertha IntHout, Ashutosh Kothari, Majid Kazmi, Amanda Clery, Yanzhong Wang, Bolaji Coker, Winnie Felix, Anita Preininger, Suwei Wang, Roy Vergis, Tom Eggebraaten, Christopher Gloe, Irene Dankwa-Mullan, Gretchen Jackson, Anna Rigg, Danny Ruta. Augmentation of a minimal multidisciplinary tumor board with clinical decision support to triage breast cancer patients in the UK [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-22.

Difficulties in diagnostics of lung tumours in biopsies: an interpathologist concordance study evaluating the international diagnostic guidelines

AimsAccurate and reliable diagnosis is essential for lung cancer treatment. The study aim was to investigate interpathologist diagnostic concordance for pulmonary tumours according to WHO diagnostic criteria.MethodsFifty-two unselected lung and...

Massively parallel sequencing of 25 short tandem repeat loci including the SE33 marker in Koreans.

Massively parallel sequencing (MPS) technology has recently been introduced in research, clinical diagnostics, and forensics. MPS enables determination of the genotypes of multiple short tandem repeat (STR) markers and to determine nucleotide sequence variations, additionally. To improve STR analysis and a paternity index, a new, smaller-sized STR panel was designed that includes the SE33 locus. This study performed MPS using an STR panel including the SE33 marker in 101 Koreans. The concordance study was conducted by comparing the data obtained from the MPS assay with the results of a capillary electrophoresis (CE)-based method. In this study, an in-house MPS panel is designed that incorporates the 20 Combined DNA Index System (CODIS) loci and the Penta D, Penta E, and SE33 markers for enhanced discriminatory ability. The data obtained via MPS analysis were compared with CE data to confirm concordance. Fifty previously unreported alleles were detected through the MPS analysis. Three new SNP variations in the flanking region were also identified. Statistical analysis demonstrated that the SE33 marker was most effectively determined the match probability (PM) and typical paternity index (TPI). In the sensitivity study, concentrations as low as 80pg could be used to obtain full and concordant profiles. We designed a new, smaller-sized STR panel that includes the SE33 locus to improve STR analysis and the paternity index. Various new alleles were identified in SE33, indicating a high degree of polymorphism. The panel is expected to provide valid data for discrimination of unidentified bodies.

Using cfRNA as a tool to evaluate clinical treatment outcomes in patients with metastatic lung cancers and other tumors.

Aim: We report an exploratory analysis of cfRNA as a biomarker to monitor clinical responses in non-small cell lung cancer (NSCLC), breast cancer, and colorectal cancer (CRC). An analysis of cfRNA as a method for measuring PD-L1 expression with comparison to clinical responses was also performed in the NSCLC cohort. Methods: Blood samples were collected from 127 patients with metastatic disease that were undergoing therapy, 52 with NSCLC, 50 with breast cancer, and 25 with CRC. cfRNA was purified from fractionated plasma, and following reverse transcription (RT), total cfRNA and gene expression of PD-L1were analyzed by real-time polymerase chain reaction (qPCR) using beta-actin expression as a surrogate for relative amounts of cfDNA and cfRNA. For the concordance study of liquid biopsies and tissue biopsies, the isolated RNA was analyzed by RNAseq for the expressions of 13 genes. We had to close the study early due to a lack of follow-up during the Covid-19 pandemic. Results: We collected a total of 373 blood samples. Mean cfRNA PCR signals after RT were about 50-fold higher than those of cfDNA. cfRNA was detected in all patients, while cfDNA was detected in 88% of them. A high concordance was found for the expression levels of 13 genes between blood and solid tumor tissue. Changes in cfRNA levels followed over the course of treatments were associated with response to therapy, increasing in progressive disease (PD) and falling when a partial response (PR) occurred. The expression of PD-L1 over time in patients treated with immunotherapy decreased with PR but increased with PD. Pre-treatment levels of PD-L1 were predictive of response in patients treated with immunotherapy. Conclusion: Changes in cfRNA correlate with clinical response to the therapy. Total cfRNA may be useful in predicting clinical outcomes. PD-L1 gene expression may provide a biomarker to predict response to PD-L1 inhibition.

Evaluación del Compromiso Cardiovascular en niños en diálisis mediante el Índice de Masa Ventricular Izquierdo

Existe una estrecha relación entre enfermedad renal crónica (ERC) y enfermedad cardiovascular. Una de sus manifestaciones clínicas es la hipertrofia de ventrículo izquierdo (HVI), expresada como Indice de Masa Ventricular Izquierda (IMVI, gr/m2.7). En pacientes portadores de ERC con retraso de crecimiento, el cálculo de IMVI debería ajustarse corrigiendo la edad para la talla.Objetivo: Comparar el IMVI corregido por edad para la talla, con el valor calculado por edad cronológica en niños con ERC en diálisis.Pacientes y Método: Estudio de corte transversal. Se analizan ecocardiografías de pacientes portadores de ERC en diálisis entre 1-18 años, enero de 2016 a julio 2017. Se evalua IMVI ajustando el valor expresado a gr/m2.7 al percentil para la edad cronológica del niño, y luego se ajusta el valor a la edad corregida por la talla. Se usa estadística descriptiva y estudio de concordancia para las evaluaciones de IMVI calculado por edad cronológica y para edad corregida por talla.Resultados: Se incluyeron 26 pacientes, 75 ecocardiogramas. Un 56% presentó HVI usando IMVI calculado por edad cronológica vs un 46,6% al corregir la edad para la talla. Al comparar los grupos de percentiles de IMVI-edad cronológica vs IMVI ajustado a la edad para la talla real, se observó que el 18,6% de la muestra cambia de grupo de percentil, el 100% de ellos a un grupo de percentil inferior. La concordancia evaluada en base a coeficiente Kappa fue de 0,72 (concordancia perfecta > 0,8), confirmando diferencias al ajustar el IMVI para la edad corregida por la talla.Conclusión: El cálculo de IMVI por edad cronológica sobreestima el compromiso cardiovascular en niños con ERC que característicamente tienen un retraso de talla. Los resultados sugieren que el cálculo de IMVI ajustado a la edad corregida por talla otorga mayor precisión al diagnóstico de hipertrofia ventricular izquierda en este grupo de pacientes.

Left Ventricular Mass Index and Cardiovascular Compromise in children on dialysis

There is a close relationship between chronic kidney disease (CKD) and cardiovascular disease. One of its clinical manifestations is left ventricular hypertrophy (LVH), expressed as Left Ventricular Mass Index (LVMI gr/m27). In CKD patients with growth retardation, the LVMI calculation should be adjusted by correcting age for length/height. To compare the age-corrected LVMI for length/height with the value calculated by chronological age in CKD children on dialysis. Cross-sectional study. We analyzed echocardiographies of CKD children on dialysis aged between 1 and 18, from January 2016 to July 2017. LVMI was evaluated by adjusting the value expressed in gr/m27 to the percentile for the chronological child's age, and then the value was adjusted to the age-corrected length/height. We used descriptive statistics and concordance study for LVMI assessments calculating by chronological age and for age-corrected length/height. 26 patients were included and 75 echocardiograms. 56% had left ventricular hypertrophy using chronological age versus 46.6% age-corrected LVMI for length/height. When comparing the percentile groups of LVMI-chronological age vs. age-adjusted LVMI for actual length/height, it was observed that 18.6% of the sample changed percentile groups, 100% of them to a lower percentile group. The agreement evaluated based on the Kappa coefficient was 0.72 (perfect agreement > 0.8), confirming differences when adjusting the LVMI for age-corrected length/height. Calculating LVMI by chro nological age overestimates the cardiovascular involvement in children with CKD who are charac teristically stunted. The results suggest that the age-adjusted, length/height-corrected calculation of LVMI gives greater accuracy to the diagnosis of left ventricular hypertrophy in this group of patients.

Comparison of Sequence Specific Primers in the Next Generation Sequencing in Human Leukocyte Antigen Typing for Transplant Recipients.

To compare two human leukocyte antigen (HLA) typing methods, namely sequence specific primers (SSP) and next generation sequencing (NGS) for alleles concordance Study Design: Descriptive study. Immunology department, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from December 2019 to May 2020. A total of 48 subjects, including 30 males and 18 females, were typed by NGS at 7 loci, making a total of 672 types loci. SSP typing was done for 276 loci among these. Comparison was made at SSP level of low resolution. NGS typing was done with Illumina's MiSeq instrument using Omixon HLA holotype 7 loci kit and analysis done with HLA twin software. SSP typing was done with micro SSP kit from onelambda. Statistical analysis was done using statistical package for social sciences (SPSS) version 24.0. Among the 672 NGS types loci and 276 SSP types loci, there were mismatches at one B locus and one C locus, whereby NGS computed HLA-B*58:01 and HLA-C*12:02 while SSP detected HLA-B*57 and HLA-C*05, respectively. At remaining 274 loci, HLA typing fully matched at low resolution, making concordance rate 99.3%. Commonest alleles detected by NGS were HLA-A*02:01, B*51:01, C*07:02, DPB1*04:01, DQA1*01:03, DQB1*02:01 and DRB1*13:01. Batch testing, high throughput, improved accuracy, more loci coverage, maximum gene coverage including all exons and introns and high-resolution typing confer significant advantages to next generation sequencing over old methods of HLA typing. This technique is suitable for high throughput laboratories. High running cost hampers its routine implementation in 3rd world countries. Key Words: Human leukocyte antigen, Next generation sequencing, High resolution.

Diagnostic imaging concordance study: Are traction radiographs necessary in a hip fracture?

Hip fractures are a pathology that have emerged as a major subject over the years, due to increased prevalence and the multiple surgical treatments involved. The characterization and classification of the lesion is essential for proper surgical planning, with anteroposterior (AP), lateral and traction radiograph of the hip, paramount for decision-making. This is a retrospective concordance study of 64 patients with hip fracture who consulted the hospital between January and July 2017. Four radiographs were taken of each: AP, AP with traction, lateral and lateral with traction. This set of images was evaluated by 9 observers, with different levels of experience, to answer questions regarding the classification, emphasize in potential instability and requirement of other images. A statistical analysis of concordance between and within observers was performed using Cohen's kappa coefficient. Of the 64 patients, 70.6% were women; the average age was 69.5 years. 82.8% presented a secondary fracture from falling from their own height. As the observer's experience increases, the need for traction radiograph decreases; interobserver kappa goes from 0.98 in experts to 0.01 in students. Traction radiograph is important in the diagnosis of potentially unstable fractures. Of the 1,503 radiographs with traction, 636 (42.38%) were classified as potentially unstable. And of the 708 without traction, 560 (79.1%) were classified as potentially unstable. Traction hip radiograph continues to be a useful tool in training environments to adequately classify an intertrochanteric fracture, considering it is a low-cost, minimal morbidity intervention, and is easily accessible. In similar studies, we found similar findings regarding the usefulness of traction to perform an adequate classification in people in training or in young orthopedists. It also influences to determine the potential instability, and this would modify the choice of the implant.

Development and validation of a custom panel including 183 Y‐SNPs for Chinese Y‐chromosomal haplogroups dissection using a MALDI‐TOF MS system

Y-chromosome SNP haplogroups exhibit geographic structuring in many populations around the world. Therefore, Y-chromosome haplogroups have been widely used to infer paternal biogeographical ancestry and high-resolution paternal lineage classification. In the present study, we designed a customized panel containing 183 Y-SNPs based on previous studies and evaluated the genotyping performance and repeatability, concordance, sensitivity, and ability of analysing case-type samples using a MALDI-TOF MS platform. The average call rate for duplicate typing of any one SNP in the panel was 97.0%. In the concordance and accuracy study, the results of haplogroup designation obtained from MALDI-TOF MS platform were fully consistent with those obtained from the next-generation sequencing (NGS) platform. The optimal amount of template DNA in the PCR seemed to be 10ng. However, if less DNA (≥156.25pg) was available, it was still possible to obtain meaningful haplogroup information. For the application part, this panel could be applied for the detection of blood, semen, and buccal swabs samples. Particularly, blood stain on FTA card samples could be dissected by direct PCR amplification on the MALDI-TOF MS platform. Besides, 371 unrelated male individuals from four Chinese ethnic groups (Han, Hui, Mongolian, and Kazak) were detected using this panel. Total 78 terminal haplogroups were found and the haplogroup diversity was 0.933576. The results demonstrate that this panel could be an accurate, fast, and cost-effective method for database construction where the amount of sample material is less of a concern and when the cost of the assay is taken into consideration.

Impact of Pre-Analytical Factors on MSI Test Accuracy in Mucinous Colorectal Adenocarcinoma: A Multi-Assay Concordance Study.

Immunohistochemistry (IHC) and polymerase chain reaction (PCR) and fragment separation by capillary electrophoresis represent the current clinical laboratory standard for the evaluation of microsatellite instability (MSI) status. The importance of reporting MSI status in colorectal cancer is based on its potential for guiding treatment and as a prognostic indicator. It is also used to identify patients for Lynch syndrome testing. Our aim was to evaluate pre-analytical factors, such as age of formalin-fixed and paraffin-embedded (FFPE) block, neoplastic cell percentage, mucinous component, and DNA integrity, that may influence the accuracy of MSI testing and assess the concordance between three different MSI evaluation approaches. We selected the mucinous colorectal cancer (CRC) histotype for this study as it may possibly represent an intrinsic diagnostic issue due to its low tumor cellularity. Seventy-five cases of mucinous CRC and corresponding normal colon tissue samples were retrospectively selected. MMR proteins were evaluated by IHC. After DNA quality and quantity evaluation, the Idylla™ and TapeStation 4200 platforms were adopted for the evaluation of MSI status. Seventy-three (97.3%) cases were successfully analyzed by the three methodologies. Overall, the Idylla™ platform showed a concordance rate with IHC of 98.0% for microsatellite stable (MSS)/proficient MMR (pMMR) cases and 81.8% for MSI/deficient MMR (dMMR) cases. The TapeStation 4200 system showed a concordance rate with IHC of 96.0% for MSS/pMMR cases and 45.4% for MSI/dMMR cases. The concordance rates of the TapeStation 4200 system with respect to the Idylla™ platform were 98.1% for MSS profile and 57.8% for MSI profile. Discordant cases were analyzed using the Titano MSI kit. Considering pre-analytical factors, no significant variation in concordance rate among IHC analyses and molecular systems was observed by considering the presence of an acellular mucus cut-off >50% of the tumor area, FFPE year preparation, and DNA concentration. Conversely, the Idylla™ platform showed a significant variation in concordance rate with the IHC approach by considering a neoplastic cell percentage >50% (p-value = 0.002), and the TapeStation 4200 system showed a significant variation in concordance rate with the IHC approach by considering a DNA integrity number (DIN) ≥4 as cut-off (p-value = 0.009). Our data pinpoint a central role of the pre-analytical phase in the diagnostic outcome of MSI testing in CRC.

Use of the new MultiColour SPECTRALIS® software for identifying retinal nerve fibre layer defects

The classical fiber photography traditionally used to identify defects in the retinal nerve fiber layer (RNFL), has been partially discontinued due to poor availability. The new Multicolour module of Spectralis Optical Coherence Tomography (OCT), using three different laser wavelengths simultaneously, can provide images that identify the structures of the retina in different colours according to their depth. A small concordance study was conducted to determine the usefulness of the new Multicolour software versus traditional fiber photography in identifying RNFL defects. The inter-observer agreement in the interpretation of Multicolour images was good (ĸ = 0.746; P < .001), as by using Multicolour they were able to identify around 70% of patients with mild glaucoma. It is believed that the new Multicolour software is useful in evaluating RNFL defects, and is easy to perform. La fotografía de fibras clásica, usada tradicionalmente para identificar defectos en la capa de fibras nerviosas de la retina (CFNR), tiene un uso limitado debido a la necesidad de un equipo fotográfico específico y un técnico experto en la adquisición de esta clase de imágenes. El nuevo módulo Multicolor de la tomografía de coherencia óptica (OCT) Spectralis, utilizando tres longitudes de onda diferentes simultáneamente, es capaz de proporcionar imágenes en las que se identifican las estructuras de la retina en diferente color según su profundidad. Nos propusimos realizar un pequeño estudio de concordancia para determinar la utilidad del nuevo software Multicolor frente a la fotografía de fibras tradicional en la identificación de defectos en la CFNR. La concordancia interobservador en la interpretación de imágenes Multicolor fue buena (ĸ = 0,746; P < ,001); y se consiguieron identificar con Multicolor en torno al 70% de pacientes con glaucoma leve. Consideramos que el nuevo software Multicolor resulta útil en la evaluación de defectos de la CFNR, y es sencillo de realizar.

Utilidad y eficiencia de la teledermatoscopia en el manejo del cáncer de piel en atención primaria

ObjectiveTo evaluate the usefulness of teledermoscopy as a diagnostic and triage method for suspected skin cancer lesions between Primary Care and Dermatology. To analyse the reduction in the number of referrals and estimate the savings achieved. Material and methodsConcordance study on a non-randomised case series. Descriptive observational study of teleconsultations sent from two Health Centres (urban and rural) to the reference Dermatology service in Cordoba (Spain) between January 2017 and April 2019.The diagnoses proposed by Primary Care before and after the use of dermatoscopy, and the diagnosis of the Dermatologist, along with other epidemiological variables were collected. Descriptive analysis and concordance study were performed. ResultsA total of 395 teleconsultations were made. The coefficient of agreement between the diagnoses of both specialists without using dermoscopy was 0.486. Using this technique the concordance was 0.641. A reduction in the number of referrals to Dermatology was 58%. A savings of 2,475€ in transfers by ambulance and 550 working hours were made. The most common diagnoses were basal cell carcinoma (20%; n=79) and seborrheic keratosis (15.2%; n=60). ConclusionsThe addition of dermoscopy increases diagnosis concordance. Teledermatology is a useful system for patient triage and for decreasing the demand for hospital care, with an inherent resources saving.

Abstract 724: Application of oncoMonitor™ ctDNA tracking technology for monitoring of therapy and early detection of recurrence in metastatic colorectal cancer

Abstract Introduction: Liquid biopsy based on detection of circulating tumor DNA (circulating-tumor DNA, ctDNA) is finding new applications in clinical management of solid cancers. From the initial use as an alternative to classical tissue biopsy for investigation of molecuar profiles in prediction or resistance detection of targeted therapies the approach is now applied to monitoring of minimal residual disease (MRD). Patients with metastatic colorectal cancer undergoing liver resection are subject to standard post-operative surveillance based mainly on periodic CT or PET/CT imaging (complemented eventually by MR imaging). Some reports have previously demonstrated benefit from performing a ctDNA detection complimentary to standard imaging to improve follow-up efficiency. Methods: In this report we demonstrate use of our oncoMonitor™ ctDNA technology, based on detection of somatic mutations derived from tumor in patient plasma. Unlike various approaches targeting oncogenic hotspot mutants, this technology can trace virtually any somatic mutation found in any gene (e.g. a tumor supressor). The relatively simple approach is based on rapid scanning of 100 to 140bp target amplicons for presence of mutations revealed based on differential melting by high-resolution denaturing capillary electrophoresis (DCE). The detection sensitivity is 0.1% MAF. Patients: In our concordance study during which a total of 41 patients with metatatic colorectal cancer were followed for 3 years from metastasectomy. oncoMonitor™ tast was applied to evaluate ctDNA along with standard CT or PET/CT imaging and tumor markers (CEA/CA19-9). Results: A total of 23 recurrences were clinically confirmed during surveillance. All recurrences were detected by oncoMonitor™ (23/23, 100%), while at the same time only 17 instances were detected by CT or PET/CT imaging (17/23, 73.9%) and 16 by tumor markers CEA/CA19-9 (16/23, 69.6%). There were 2 patients after R0 resection with persistent ctDNA positivity who had recurrence within 6 months from surgery. Conclusions: oncoMonitor™ technology is suitable for quick and sensitive detection of ctDNA in plasma of patients with metatatic colorectal cancer after liver resection. Evaluation of ctDNA presence improves efficiency of post-operative surveillance. Supported by Czech Ministry of Health project no. 17-31909A. Citation Format: Marek Minarik, Barbora Belsanova, Renata Ptackova, Tereza Halkova, Filip Pazdirek, Jiri Pudil, Miroslav Levy, Jaromir Simsa, Jiri Hoch, Miroslav Ryska, Lubos Petruzelka, Lucie Benesova. Application of oncoMonitor™ ctDNA tracking technology for monitoring of therapy and early detection of recurrence in metastatic colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 724.

What are the implications of using individual and combined sources of routinely collected data to identify and characterise incident site-specific cancers? a concordance and validation study using linked English electronic health records data

ObjectivesTo describe the benefits and limitations of using individual and combinations of linked English electronic health data to identify incident cancers.Design and settingOur descriptive study uses linked English Clinical Practice...

Consistency between anticholinergic burden scales in patients with Sjögren's syndrome

IntroductionSjögren's syndrome is the second most frequent autoimmune rheumatic disease and is characterized by exocrine gland involvement manifesting as sicca symptoms. The objective of this study was to estimate the degree of agreement between three anticholinergic burden scales related to the prescriptions of patients diagnosed with Sjögren's syndrome in Colombia. Materials and methodsAn analytical concordance study was conducted. The weighted kappa coefficient with quadratic weights was used to identify consistency between the Anticholinergic Drug Scale (ADS), Anticholinergic Cognitive Burden Scale (ACB) and Anticholinergic Risk Scale (ARS), which address the prescriptions used for 3 months by patients with Sjögren's syndrome, in a population database. ResultsA total of 15,696 patients with Sjögren's syndrome were identified, with a mean age of 65.4±13.9 years, and 74.2% were women. A total of 94.1% of the patients received at least one topical lubricant, with carboxymethyl cellulose being the most commonly prescribed (22.9%), while oral pilocarpine was prescribed to 3.5% of patients. The ACB was the tool identified more antimuscarinic prescriptions (37.5%), followed by the ADS (35.3%) and ARS (25.2%). The greatest degree of agreement was found between the ADS and ACB (kappa 0.6520; confidence interval (CI): 0.6393–0.6648). ConclusionsExcept for the ADS and ACB, little agreement was found between the three scales gauging the anticholinergic burden. Additional studies are needed to determine how these differences can impact the clinical outcomes of patients.

Heritability of tanning addiction: A twin concordance study

To the Editor: Tanning addiction is a dermatologic-psychiatric disorder with characteristics of behavioral addiction, substance use disorder, and other psychiatric disorders. Minimal information exists regarding the unique contribution of genetic components and environmental exposures to tanning addiction. The objective of this study was to estimate concordance rates and heritability of tanning addiction in a twin cohort.

Multiple Electrode Aggregometry After Cardiopulmonary Bypass to Assess Platelet (Dys)-Function and Transfusion Threshold: A Concordance Study

Cardiac surgery patients have a high risk of postoperative bleeding. Historically, the platelet count has been one of the main parameters used to establish the need for platelet transfusions, and the recent introduction of point-of-care tests for platelet function has allowed clinicians to rationalize platelet transfusion needs by assessing the platelet (dys-)function of the patient. For the present study, the authors evaluated how the introduction of one of these systems-the adenosine diphosphate (ADP) test, performed using a Multiplate electrode analyzer (Roche Diagnostics, Basel, Switzerland)-into their clinical practice had modified their platelet transfusion practice. The relationship between the platelet count and the functional evaluation of platelet aggregation (via the ADP test) also was examined. This was a retrospective, single-center, observational study. Cardiac surgery department of a tertiary care center in North-east Italy. Cardiac surgery patients requiring cardiac bypass in 2017 and 2019. The primary outcome was to compare platelet transfusion practice before and after the implementation of a platelet function test (the ADP test) into the institution's transfusion algorithm, which replaced the platelet count as the trigger. Secondary outcomes were assessing whether the incorporation of the ADP test into their transfusion algorithm brought about a reduction in the frequency of platelet transfusions compared with previous rates (when only platelets counts were used); assessing patient blood loss in the first 12 postoperative hours; and ascertaining the percentage of patients requiring surgical reexplorations. The study comprised 110 patients undergoing cardiac surgery from the platelet count period (2017) and 110 patients from the ADP test period (2019). Agreement between platelet counts versus ADP tests in determining the need for platelet transfusion was moderate (κ = 0.483; 95% confidence interval [CI] 0.239-0.728), and the general linear regression relationship between platelet counts and the ADP test (Akaike information criterion = 2536; p < 0.001) was determined. Since the introduction of ADP testing, a highly significant reduction in platelet transfusions has occurred: 41.82% (platelet count period) versus 13.64% (ADP test period) (p < 0.001); average blood loss in the 12 hours postsurgery also was less in the ADP test period (p < 0.001) at 300 mL (95% CI 150-730) compared with 440 mL in the platelet count period (95% CI 135-900). Furthermore, a decreasing trend was observed in the number of patients requiring reexploration to optimize hemostasis in the first 12 hours postsurgery (6.36% v 2.73%); however, this trend did not achieve statistical significance (p = 0.195). The application of new Multiplate analyzer technologies, like the ADP test, have the potential to reduce platelet transfusion rates in cardiac surgery patients compared with the use of platelet counts alone; this point-of-care test may constitute an important strategy to help spare the use of allogeneic blood products. Additional studies are needed to confirm this trend and establish the best cutoff values to apply.