Richard Gray

Validation Study of a Quantitative Multigene Reverse Transcriptase–Polymerase Chain Reaction Assay for Assessment of Recurrence Risk in Patients With Stage II Colon Cancer

PURPOSE We developed quantitative gene expression assays to assess recurrence risk and benefits from chemotherapy in patients with stage II colon cancer. PATIENTS AND METHODS We sought validation by using RNA extracted from fixed paraffin-embedded primary colon tumor blocks from 1,436 patients with stage II colon cancer in the QUASAR (Quick and Simple and Reliable) study of adjuvant fluoropyrimidine chemotherapy versus surgery alone. A recurrence score (RS) and a treatment score (TS) were calculated from gene expression levels of 13 cancer-related genes (n = 7 recurrence genes and n = 6 treatment benefit genes) and from five reference genes with prespecified algorithms. Cox proportional hazards regression models and log-rank methods were used to analyze the relationship between the RS and risk of recurrence in patients treated with surgery alone and between TS and benefits of chemotherapy. RESULTS Risk of recurrence was significantly associated with RS (hazard ratio [HR] per interquartile range, 1.38; 95% CI, 1.11 to 1.74; P = .004). Recurrence risks at 3 years were 12%, 18%, and 22% for predefined low, intermediate, and high recurrence risk groups, respectively. T stage (HR, 1.94; P < .001) and mismatch repair (MMR) status (HR, 0.31; P < .001) were the strongest histopathologic prognostic factors. The continuous RS was associated with risk of recurrence (P = .006) beyond these and other covariates. There was no trend for increased benefit from chemotherapy at higher TS (P = .95). CONCLUSION The continuous 12-gene RS has been validated in a prospective study for assessment of recurrence risk in patients with stage II colon cancer after surgery and provides prognostic value that complements T stage and MMR. The TS was not predictive of chemotherapy benefit.

Safer non-cardiac surgery for patients with coronary artery disease : Medical treatment should be optimised to improve outcome

How best to manage patients with coronary artery disease who undergo major non-cardiac surgery is an increasingly important issue as the populationages. Such patients, particularly those with easily induced ischaemia, are at increased risk of perioperative cardiac complications and death.1 Various pre-emptive interventions have beenconsidered to minimise this risk, but often their precise role is poorly defined. Coronary artery bypass grafting is effective but carries its own risks, and overall survival benefit is seen only in patients who warrant bypass surgery independently of their major non-cardiac operation.2 These patients, although few, are a well defined3 population who should be offered prophylactic coronary revascularisation. The role of percutaneous transluminal coronary angioplasty is less well defined because, even in the wider populationof patients with coronary artery disease, no prospective randomised trial has shown a prognostic benefit for angioplasty over medical treatment. Use of preoperative angioplasty should therefore be restricted to patients with readily inducible ischaemia, in whom a single coronary stenosis subtends a large area of viable myocardium.4 Most patients with coronary artery disease presenting for elective …

Remission Induction and Postremission Therapy in Acute Myelogenous Leukemia: British MRC Study

At the first International Symposium on Acute Leukaemias — Prognostic Factors and Treatment Strategies in 1986, we outlined the background and preliminary results of the Ninth MRC AML trial. The protocol is summarised in Fig. 1. The trial closed for patients under 55 years of age in July 1988 but remains open for older patients.

The ninth British Medical Research Council trial for the treatment of acute myeloid leukaemia.

The Ninth British Medical Research Council trial for the treatment of acute myeloid leukaemia (AML) opened in February 1984 to all patients with primary or secondary forms of the disease; there was no age limit. Patients were randomised to receive either a 1 + 5 DAT combination (daunorubicin 50 mg/m2 i.v. on day 1, cytosine arabinoside 100 mg/m2 i.v. every 12 h on days 1–5, and 6-thioguanine 100 mg/m2 every 12 h on days 1–5) or a 3 +10 DAT regime (daunorubicin at the same dose on days 1, 3, and 5 and cytosine arabinoside and 6-thioguanine again at the same doses as in the 1 + 5 combination but on days 1–10).