RAS assessment is mandatory for therapy decision in metastatic colorectal cancer (mCRC) patients. This determination is based on tumor tissue, however, genotyping of circulating tumor (ct)DNA offers ...clear advantages as a minimally invasive method that represents tumor heterogeneity. Our study aims to evaluate the use of ctDNA as an alternative for determining baseline RAS status and subsequent monitoring of RAS mutations during therapy as a component of routine clinical practice.
RAS mutational status in plasma was evaluated in mCRC patients by OncoBEAM™ RAS CRC assay. Concordance of results in plasma and tissue was retrospectively evaluated.RAS mutations were also prospectively monitored in longitudinal plasma samples from selected patients.
Analysis of RAS in tissue and plasma samples from 115 mCRC patients showed a 93% overall agreement. Plasma/tissue RAS discrepancies were mainly explained by spatial and temporal tumor heterogeneity. Analysis of clinico-pathological features showed that the site of metastasis (i.e. peritoneal, lung), the histology of the tumor (i.e. mucinous) and administration of treatment previous to blood collection negatively impacted the detection of RAS in ctDNA. In patients with baseline mutant RAS tumors treated with chemotherapy/antiangiogenic, longitudinal analysis of RAS ctDNA mirrored response to treatment, being an early predictor of response. In patients RAS wt, longitudinal monitoring of RAS ctDNA revealed that OncoBEAM was useful to detect emergence of RAS mutations during anti-EGFR treatment.
The high overall agreement in RAS mutational assessment between plasma and tissue supports blood-based testing with OncoBEAM™ as a viable alternative for genotyping RAS of mCRC patients in routine clinical practice. Our study describes practical clinico-pathological specifications to optimize RAS ctDNA determination. Moreover, OncoBEAM™ is useful to monitor RAS in patients undergoing systemic therapy to detect resistance and evaluate the efficacy of particular treatments.
Circulating tumor DNA (ctDNA) is a potential source for tumor genome analysis. We explored the concordance between the mutational status of RAS in tumor tissue and ctDNA in metastatic colorectal ...cancer (mCRC) patients to establish eligibility for anti-epidermal growth factor receptor (EGFR) therapy.
A prospective-retrospective cohort study was carried out. Tumor tissue from 146 mCRC patients was tested for RAS status with standard of care (SoC) PCR techniques, and Digital PCR (BEAMing) was used both in plasma and tumor tissue.
ctDNA BEAMing RAS testing showed 89.7% agreement with SoC (Kappa index 0.80; 95% CI 0.71 − 0.90) and BEAMing in tissue showed 90.9% agreement with SoC (Kappa index 0.83; 95% CI 0.74 − 0.92). Fifteen cases (10.3%) showed discordant tissue-plasma results. ctDNA analysis identified nine cases of low frequency RAS mutations that were not detected in tissue, possibly due to technical sensitivity or heterogeneity. In six cases,RAS mutations were not detected in plasma, potentially explained by low tumor burden or ctDNA shedding. Prediction of treatment benefit in patients receiving anti-EGFR plus irinotecan in second- or third-line was equivalent if tested with SoC PCR and ctDNA. Forty-eight percent of the patients showed mutant allele fractions in plasma below 1%.
Plasma RAS determination showed high overall agreement and captured a mCRC population responsive to anti-EGFR therapy with the same predictive level as SoC tissue testing. The feasibility and practicality of ctDNA analysis may translate into an alternative tool for anti-EGFR treatment selection.
Solitary fibrous tumour of the pleura Sikri, V; Chawla, R
Indian journal of chest diseases & allied sciences,
2013 Jul-Sep, Letnik:
55, Številka:
3
Journal Article
Recenzirano
Solitary fibrous tumour (SFT) of the pleura is a rare, usually benign primary tumour of the pleura. Spectrum of presentation can vary from an incidental finding on chest radiograph done for some ...other purpose, features of compression of surrounding structures to symptoms resulting from the tumour per se. We report a case of a female who presented with complaints of cough and chest pain in whom a diagnosis of SFT was confirmed on tru-cut biopsy and immunohistochemistry studies. The patient underwent thoracotomy and successful removal of the tumour.
One hundred and twelve mandibular first premolars and ninety six mandibular second premolars were studied to evaluate morphological aberrations in their pulp spaces. Each tooth was radiographed from ...two direct ions viz. buccolingual and mesiodistal and was sectioned at three sites, cementoenamel junction, middle third and apical third. 29.5%, mandibular first premolar & 13.5% mandibular second premolar exhibited second root canal with 44.60% & 46.9% curvatures respectively. Oval shape of the canal was most prevalent at cervical third area while the canal became round at middle and apical third areas. Approximately 10% mandibular first premolar exhibited C-shaped canal, while this shape was not observed in mandibular second premolar. It is concluded from this study that the knowledge of possible aberrations always help dentist realize and manage the root canal system in a better way.
Twenty one posterior teeth were selected at random from patients visiting outpatient Department of Punjab Govt. Dental College and Hospital, Amritsar. Out of twenty one treated teeth, seventeen had ...definite radiolucent area at periapex, three were non vital with no periapical radiolucent area and one tooth was vital with pulp exposure. All the teeth were treated with resinifying therapy. The treated teeth were examined after 3 months, 6 months and 9 months as regards pain on percussion, swelling and/or sinus formation. The teeth were radiographed on each follow up and the decrease/increase in radiolucency at the periapex were noted. Clinically all the treated teeth responded normal except for one which showed sinus formation after three months period of observation. This tooth was, however, retreated. Radiologically, the success rate after 9 months of observations was 84.1%. However, mean decrease in radiolucency was 2.1 mm after 3 months, 4.0 after 6 months and 5.8 after 9 months. Resinifying therapy is strongly advocated for posterior teeth with large periapical areas and also for vital teeth with pulp exposure where root canal therapy can be completed in single visit. Furthermore, the mechanism, indications and contraindication of this therapy are also discussed.
Myxoid leiomyoma is an extremely rare tumor, presenting as a scrotal mass. We report a case of 60 years male, who presented with a painless scrotal mass and operated as secondary hydrocoele. This ...lesion should be differentiated from other myxoid tumors and tumors with myxoid degeneration.
This study was undertaken to find out the prevalence of overhanging Cl. II silver amalgam restorations amongst patients visiting Pb. Govt. Dental College and Hospital, Amritsar and Govt. Dental ...College Hospital, Patiala. Two parameters viz. the pocket depth and the extent of bone loss were evaluated to study the after effects of the overhanging restorations. The findings of this investigation showed the alarming prevalence of overhanging restorations (64.12%) and clearly indicate the relationship of overhangs with periodontal diseases. Periodontal breakdown was more evident along with overhanging restorations as compared to unrestored contralateral teeth. The mean pocket depth in restored surfaces was 3.75 mm as compared to 3.46 mm in unrestored ones, showing 8.38% increase. The mean extent of bone loss in restored tooth surface was 1.64 mm as compared to 1.50 mm in unrestored ones, showing an increase of 9.33%.
PDF
