Impact of Prosigna test on adjuvant treatment decision in lymph node-negative early breast cancer-a prospective national multicentre study (EMIT-1).

BACKGROUND: EMIT-1 is a national, observational, single-arm trial designed to assess the value of the Prosigna, Prediction Analysis of Microarray using the 50 gene classifier (PAM50)/Risk of Recurrence (ROR), test as a routine diagnostic tool, examining its impact on adjuvant treatment decisions, clinical outcomes, side-effects and cost-effectiveness. Here we present the impact on treatment decisions. PATIENTS AND METHODS: Patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative pT1-pT2 lymph node-negative early breast cancer (EBC) were included. The Prosigna test and standard histopathology assessments were carried out. Clinicians' treatment decisions were recorded before (pre-Prosigna) and after (post-Prosigna) the Prosigna test results were disclosed. RESULTS: Of 2217 patients included, 2178 had conclusive Prosigna results. The pre-Prosigna treatment decisions were: no systemic treatment (NT) in 27% of patients, endocrine treatment alone (ET) in 38% and chemotherapy (CT) followed by ET (CT + ET) in 35%. Post-Prosigna treatment decisions were 25% NT, 51% ET and 24% CT + ET, respectively. Adjuvant treatment changed in 28% of patients, including 21% change in CT use. Among patients assigned to CT + ET pre-Prosigna, 45% were de-escalated to ET post-Prosigna. Of patients assigned to ET, 12% were escalated to CT + ET and 8% were de-escalated to NT; of those assigned to NT, 18% were escalated to ET/CT + ET. CT was more frequently recommended for patients aged ≤50 years. In the subgroup with pT1c-pT2 G2 and intermediate Ki67 (0.5-1.5× local laboratory median Ki67 score), the pre-Prosigna CT treatment decision varied widely across hospitals (3%-51%). Post-Prosigna, the variability of CT use was markedly reduced (8%-24%). The correlation between Ki67 and ROR score within this subgroup was poor (r = 0.25-0.39). The median ROR score increased by increasing histological grade, but the ROR score ranges were wide (for G1 0-79, G2 0-90, G3 16-94). CONCLUSION: The Prosigna test result changed adjuvant treatment decisions in all EBC clinical risk groups, markedly decreased the CT use for patients categorized as higher clinical risk pre-Prosigna and reduced treatment decision discrepancies between hospitals.

Resuscitative emergency thoracotomy in a Scandinavian trauma hospital--is it justified?

OBJECTIVE: Resuscitative emergency thoracotomy (ET) is of value in selected (penetrating) trauma patients. Current survival-estimates and recommended guidelines are based on data from the United States. However, reports from European trauma centres are lacking. We report the current experience from a Scandinavian trauma hospital. METHODS: Identification of all consecutive ETs performed during a 5-year period. Data on demographics, and injury severity score (ISS), mechanism and location were recorded. Physiological status on admission (revised trauma score, RTS) and probability of survival (Ps) were calculated. Signs of life (SOL) and need for closed-chest cardiopulmonary resuscitation (CC-CPR) were recorded through the post-injury phase. RESULTS: Ten patients underwent ET with no survivors. The annual incidence of ET was 0.7 per 100,000 inhabitants during the study period, with an increasing trend during the last years (r=0.74, p=0.014). ETs were performed in 0.7% of all trauma admissions, and in 2.5% of all severely injured patients (ISS>or=16). Blunt mechanism dominated; only three had penetrating injuries. Most frequent location of major injury was "multiple" (n=4) and "thoracic" (n=4). The male to female ratio was 7:3. Median age was 51 years (range 21-77). Median ISS was 34.5 (range 26-75), indicating severely injured patients, with seriously deranged physiology (median RTS of 0.0, range 0-6.1) with poor chance of survival (median Ps of 4.4%, range 0-89.5%). Males had significantly lower RTS and Ps (p=0.007 and 0.03, respectively) than females. Eight patients had signs of life at some time post-injury, but only four in the emergency room. Six patients had both pre- and in-hospital CC-CPR. Four patients had additional surgery to ET. Two possible preventable deaths were identified (Ps) of 51 and 89%), one in a third trimester pregnancy. CONCLUSION: Emergency thoracotomy is a rarely performed procedure in a rather busy Scandinavian trauma hospital, and outcome is dismal. Reevaluation of our decision-making process concerning the use of emergency thoracotomy is needed. How survival data and clinical experience in Europe compare to current figures from North America deserves further attention.

Microsatellite instability in colorectal cancer.

BACKGROUND: Microsatellite instability (MSI) causes hereditary non-polyposis colorectal cancer (HNPCC), and occurs in about 15 per cent of sporadic colorectal cancers. Although the basic mechanisms are not clear, there is increased understanding of the clinicopathological consequences of MSI. METHODS: Medline was searched for articles with a combination of keywords relating to MSI in colorectal cancer, focusing on molecular mechanisms, clinicopathological implications, and prognostic and predictive value. Emphasis was placed on articles from the past 5 years. RESULTS: The genetic mechanisms differ in hereditary (germline mutation) and sporadic (epigenetic silencing) colorectal cancer. The MSI pathway frequently has altered transforming growth factor beta receptor II and BAX genes, often beta-catenin, and occasionally p16INK4A and PTEN. Changes in K-ras, adenomatous polyposis coli and p53 are rare. Polymerase chain reaction testing for MSI is superior to immunohistochemistry, but complicated by the number and types of nucleotide markers. The Bethesda panel guides HNPCC testing, but guidelines are lacking for general screening. The presence and role of low-frequency MSI remains controversial. Tumours with MSI tend to occur in the proximal colon and be large, but they have a good prognosis. Their reduced response to adjuvant chemotherapy requires confirmation. CONCLUSION: Research on colorectal cancer needs to be stratified according to microsatellite status in order further to explore the molecular mechanisms and clinicopathological consequences of MSI.