A clinical trial should only be launched in the presence of equipoise both amongst clinicians responsible for treating the disease and their patients. However, during the period of patient recruitment the chances are that the levels of equipoise will modify. In some cases, where toxicity or inferiority of efficacy are readily demonstrable, the trial needs to be stopped prematurely to prevent harm to patients. In other cases, the degree of equipoise may be increased by the very existence of the trial or from conflicting evidence reported from other studies. By reference to four specific trials it is argued that instead of definitive rules, the decision as to whether recruitment should be continued must be the role of a Data Monitoring Committee which is able to consider and respond to all the available evidence.

Bias↗

PubMedDate not supplied

Role of radiotherapy following total mastectomy in patients with early breast cancer. The Closed Trials Working Party of the CRC Breast Cancer Trials Group.

Between June 1970 and April 1975 the CRC (King's/Cambridge) Trial for early breast cancer randomized 2800 patients following mastectomy to immediate prophylactic radiotherapy (DXT group, n = 1376) or control (WP group, n = 1424). Although no difference in overall survival has been demonstrated, there is an increase in mortality in the irradiated patients from nonbreast cancer causes beyond 5 years. It is because of an increase in the number of deaths due to new nonbreast malignancies [RR V 1.89 (1.18-3.05)] and to cardiac-related disease [RR = 1.52 (1.01-2.29)]. This increased cardiac death rate may be related to the use of orthovoltage, which has greater scatter. There was a significant increase in risk for those with left-sided rather than right-sided tumors in this subgroup [chi 2 (int) = 5.08; p = 0.02]. Local relapse was significantly reduced in those patients randomized to radiotherapy [RR = 0.44 (0.39-0.51)]. Median survival following local relapse was 1.35 years in the DXT group and 2.66 years in the WP group (logrank p < 0.001). Patients with the first relapse in the supraclavicular nodes had a particularly poor prognosis (median survival: DXT 0.69 years; WP 1.37 years). Almost 50% of patients who have had a recurrence on the chest wall or in the axilla and subsequently died have had disease at the same site at death, regardless of whether they had radiotherapy immediately following surgery. However, the actual number of patients dying with persistent disease is halved by the use of prophylactic radiotherapy (DXT 66; WP 143). Classic pathological features such as tumor size, tumor grade, and nodal involvement help define those patients at high risk of local failure who should be recommended for immediate radiotherapy.

Breast Neoplasms↗

PubMedDate not supplied

Benign breast disease: the cost of the service and the cost to the patient.

The patients attending a hospital breast clinic during 1 year have been reviewed to assess the impact and cost of benign conditions. Four of 5 patients referred do not have cancer. The cost to the patient lies predominantly in anxiety related to the possibility of cancer and, to a lesser extent, in cosmetic damage due to multiple biopsies. Benign breast disease is a common problem that creates severe anxiety in many women and a heavy burden on an overstretched National Health Service. A policy of reeducating general practitioners when it is safe not to refer may reduce this problem. Cyst aspiration or needle aspiration cytology may reduce the burden to both the patient and the health service, while desensitization of women's groups and women themselves to the needs for breast self-examination can also reduce this burden.

Breast Diseases↗

PubMedDate not supplied

The effect of hemodilution on regional myocardial function in the presence of coronary stenosis.

Hemodilution decreases blood viscosity and circulatory input impedance and thus reduces afterload. Its use in treatment of LV power failure has been advocated, but the safe limits of isovolemic hemodilution are not known. Compensation of the reduced O2-capacity of the blood was therefore studied with normal and impaired coronary reserve. In 20 dogs the LAD was stenosed to a degree just not affecting the supplied region and central and coronary hemodynamics were studied. Regional myocardial function was assessed by ultrasound transit time between transducers implanted in the LV wall. Lowering the hematocrit to 15% by isovolumic exchange of blood for Dextran 60 increased CVP (18%), PAP (47%), LAP (64%), LVedP (46%), CO (67%), and flow to the intact area (LCA: 211%). Flow in the stenosed LAD increased slightly. Enddiastolic length (EDL) of LAD dependent muscle segments rose to 120% and their contraction amplitude deltaL was decreased by 46%. Whereas non-ischemic segments showed compensatory rise in deltaL (38%) at almost constant EDL (+9%). After release of the LAD stenosis EDL and deltaL returned to normal. During progressive anemia myocardial O2-demand is not adequately met if coronary reserve capacity is depleted. Reversion of hypokinesia after removal of the stenosis shows unimpaired myocardial function at a hematocrit as low as 15% provided the coronary circulation is intact.

Animals↗