Search results for "Instability"
showing 10 items of 724 documents
Assessing molecular subtypes of gastric cancer: microsatellite unstable and Epstein-Barr virus subtypes. Methods for detection and clinical and patho…
2018
Background The molecular classification of gastric cancer recognises two subtypes prone to immune checkpoint blockade: the microsatellite unstable and the Epstein-Barr virus (EBV)-related tumours. We aim to assess the concordance between immunohistochemistry and PCR for microsatellite status evaluation, and explore the value of microsatellite instability (MSI) and EBV as predictive survival factors. Material and methods We collected 246 consecutively diagnosed gastric cancer cases in all stages and evaluated the microsatellite status using immunohistochemistry for mismatched repair (MMR) proteins and PCR. EBV expression was studied through in situ hybridisation. Results Forty-five (18%) cas…
Comparative Analyses of Two Established Scores to Assess the Stability of Spinal Bone Metastases Before and After Palliative Radiotherapy
2021
Background and PurposeTo compare two validated spinal instability scores regarding the stabilizing effects and skeletal-related events (SREs) of palliative radiotherapy (RT) in patients with spinal bone metastases (SBM).Materials and MethodsTwo hundred eighty-two osteolytic SBM of lung or breast cancer patients were analyzed for stability before and following RT based on the Spinal Instability Neoplastic Score (SINS) or the Taneichi score. Score concordance was quantified by absolute agreement and Cohen’s kappa coefficient. SREs were defined as fractures or local progression after RT. OS was quantified as the time between the start of RT and death from any cause.ResultsAt 3 and 6 months aft…
In the literature: October 2020.
2020
Immune checkpoint inhibitors are widely used as treatment for an increasing number of solid tumours. Nevertheless, the lack of predictive biomarker represents a limitation across several cancer types. During the last years, the possibility to dynamically study tumour evolution through circulating tumour DNA (ctDNA) in plasma has opened novel possibility in evaluating disease status and therapeutic response, especially in localised disease to predict the possibility of relapse. However, the specific opportunities for application in the context of immunotherapy remain to be clarified.1 In an article recently published in Cancer Discovery by Zhang et al ,2 a comprehensive analysis of ctDNA dat…
In the literature: October 2018
2018
Several trials with the check-point inhibitors pembrolizumab or nivolumab demonstrated some antitumour efficacy in chemorefractory advanced gastric cancer with a response rate ranging from 10% to 26%. However, no clear predictive biomarkers were found to facilitate a proper selection of patients. A series of 61 patients with advanced gastric cancer received second-line or third-line treatment with pembrolizumab in a prospective phase 2 trial.1 In a cooperative effort carried out by Korean and American investigators, a molecular characterisation of all tumours was performed including whole-exome sequencing and RNA sequencing of tissue biopsies, as well as circulating tumour DNA (ctDNA) from …
In the literature: December 2018
2018
The current development of immune checkpoint modulatory treatments has shown durable responses in the treatment of multiple cancer types.1 However, predictive biomarkers beyond PD-1 ligand 1 (PD-L1) expression and high microsatellite instability (MSI-H) to stratify patients and identify those who could benefit of these therapies are needed. In this sense, a recent study published in Science by Cristescu et al 2 describes the potential usefulness of combining the tumour mutational burden (TMB) and the T cell-inflamed gene expression profile (GEP) to jointly predict clinical response to pembrolizumab. Both PD-L1 and the GEP represent a T cell-inflamed tumour microenvironment (TME), whereas TM…
Distinct Mutational Profile of Lynch Syndrome Colorectal Cancers Diagnosed under Regular Colonoscopy Surveillance
2021
Regular colonoscopy even with short intervals does not prevent all colorectal cancers (CRC) in Lynch syndrome (LS). In the present study, we asked whether cancers detected under regular colonoscopy surveillance (incident cancers) are phenotypically different from cancers detected at first colonoscopy (prevalent cancers). We analyzed clinical, histological, immunological and mutational characteristics, including panel sequencing and high-throughput coding microsatellite (cMS) analysis, in 28 incident and 67 prevalent LS CRCs (n total = 95). Incident cancers presented with lower UICC and T stage compared to prevalent cancers (p <
Molecular markers and biological targeted therapies in metastatic colorectal cancer: expert opinion and recommendations derived from the 11th ESMO/Wo…
2010
The article summarizes the expert discussion and recommendations on the use of molecular markers and of biological targeted therapies in metastatic colorectal cancer (mCRC), as well as a proposed treatment decision strategy for mCRC treatment. The meeting was conducted during the 11th ESMO/World Gastrointestinal Cancer Congress (WGICC) in Barcelona in June 2009. The manuscript describes the outcome of an expert discussion leading to an expert recommendation. The increasing knowledge on clinical and molecular markers and the availability of biological targeted therapies have major implications in the optimal management in mCRC. 21 Suppl 6 vi1 10
Exome and immune cell score analyses reveal great variation within synchronous primary colorectal cancers
2019
BACKGROUND: Approximately 4% of colorectal cancer (CRC) patients have at least two simultaneous cancers in the colon. Due to the shared environment, these synchronous CRCs (SCRCs) provide a unique setting to study colorectal carcinogenesis. Understanding whether these tumours are genetically similar or distinct is essential when designing therapeutic approaches. METHODS: We performed exome sequencing of 47 primary cancers and corresponding normal samples from 23 patients. Additionally, we carried out a comprehensive mutational signature analysis to assess whether tumours had undergone similar mutational processes and the first immune cell score analysis (IS) of SCRC to analyse the interplay…
Patterns of K-ras mutation in colorectal carcinomas from Iran and Italy (a Gruppo Oncologico dell'Italia Meridionale study): influence of microsatell…
2006
Background: K-ras mutations are a key step in colorectal cancer progression. Such mutations have been widely studied in case series from Western countries but there are few data on the rate and spectrum of mutations in tumors from countries where the epidemiological features of the disease are different. Patients and methods: Tumor samples from 182 Iranian colorectal cancer patients (170 sporadic cases and 12 HNPCC cases) were screened for K-ras mutations at codons 12, 13 and 61 by sequencing analysis. The cases were also characterized for microsatellite instability at mononucleotide repeats by PCR and fragment analysis, and classified according to microsatellite instability status. The fre…
Pharmacokinetic and metabolism determinants of fluoropyrimidines and oxaliplatin activity in treatment of colorectal patients
2011
Fluoropyrimidines and oxaliplatin continued to be the mainstay of therapeutic regimens in the treatment of colorectal cancer (CRC). For this reason, pharmacokinetic and metabolism of these drugs were analyzed and the identification of accurate and validated predictive, prognostic and toxicity markers became necessary to develop an effective therapy adapted to the patient's molecular profile, while minimizing life-threatening toxicities. In this review, we discuss literature data, defining predictive and prognostic markers actually identified in the treatment of CRC. We analyzed predictive markers of fluoropyrimidines effectiveness, principally for 5-Fluorouracil (5-FU) and also for oral flu…