On Cost Effectiveness and Sample Size in Clinical Trials

Clinical-trial-design, Cost-effectiveness

Defining and categorizing leukoencephalopathies of unknown origin: MR imaging approach

PURPOSE: To categorize leukoencephalopathies of unknown origin into a few major groups by using magnetic resonance (MR) imaging criteria to facilitate further studies, and to assess the possibility of defining 'new' (ie, until now unknown) disease entities within these major groups. MATERIALS AND METHODS: MR images of 92 patients (55 male, 37 female; mean age, 9.3 years) with a leukoencephalopathy were examined by using a scoring list of 68 items. Seven major categories were defined according to the predominant location of the white matter abnormal ties. Statistical analysis was used to assess the validity of these seven categories. RESULTS: Statistical analysis results showed that the seven categories could be well distinguished by either using the defining variables initially accepted as inclusion criteria or selecting a few other variables found to have discriminating value. The additional variables confirmed that the categories are essentially distinct and vary systematically with regard to items other than the inclusion criteria. The existence of two recently defined leukoencephalopathies was confirmed, but no consistent evidence of other new disease entities could be provided. CONCLUSION: Establishing these seven categories helps in the interpretation of individual studies by demonstrating features that the patient has in common with other patients, and it may facilitate further research on homogeneous subgroups of patients and allow pooling of data across multiple centers

Pattern of White Matter Abnormalities at MR Imaging: Use of Polymerase Chain Reaction Testing of Guthrie Cards to Link Pattern with Congenital Cytomegalovirus Infection

PURPOSE: To define a magnetic resonance (MR) imaging pattern suggestive of congenital cytomegalovirus (CMV) infection by using polymerase chain reaction (PCR) testing to detect CMV DNA in neonatal blood on Guthrie cards for validation. MATERIALS AND METHODS: On the basis of findings in eight patients with documented congenital CMV infection, the authors developed MR imaging inclusion criteria, including multifocal lesions predominantly located in the deep parietal white matter. If gyral abnormalities were present, white matter lesions were either multifocal or diffuse. The criteria were applied to 152 patients with static leukoencephalopathy of unknown etiology. Guthrie cards for 22 of the 43 patients fulfilling the MR imaging criteria, 20 patients not fulfilling them, and 300 control subjects were analyzed. Fisher exact testing was used to evaluate the association between MR imaging characteristics and CMV status, and backward elimination linear discriminant analysis was used to identify MR imaging characteristics predictive of CMV infection in addition to the initial criteria. RESULTS: PCR test results were positive in 12 of 22 patients suspected of having congenital CMV infection, in no patient not suspected of having infection (P < .001), and in two of 300 control subjects (negative predictive value [NPV] of MR imaging criteria, 100% [95% CI: 83%, 100%]; positive predictive value [PPV], 55% [95% CI: 32%, 76%]). The most important additional MR imaging finding predicting a positive PCR result was abnormality of the anterior part of the temporal lobe, including abnormal white matter, cysts, and enlargement of inferior horns. Including this finding in the MR imaging criteria enhanced the PPV (89%; 95% CI: 52%, 99%) at the expense of the NPV (88%; 95% CI: 72%, 97%). CONCLUSION: In patients with static encephalopathy, an MR imaging pattern of multifocal lesions predominantly involving deep parietal white matter, with or without gyral abnormalities, is predictive of congenital CMV infection. When gyral abnormalities are present, leukoencephalopathy may also be diffuse. The presence of abnormalities in the anterior part of the temporal lobe increases the likelihood that CMV infection is present

Impact of Pathological Characteristics on Local Relapse After Breast-Conserving Therapy: A Subgroup Analysis of the EORTC Boost Versus No Boost Trial

Item does not contain fulltextPURPOSE: To investigate the long-term impact of pathologic characteristics and an extra boost dose of 16 Gy on local relapse, for stage I and II invasive breast cancer patients treated with breast conserving therapy (BCT). PATIENTS AND METHODS: In the European Organisation for Research and Treatment of Cancer boost versus no boost trial, after whole breast irradiation, patients with microscopically complete excision of invasive tumor, were randomly assigned to receive or not an extra boost dose of 16 Gy. For a subset of 1,616 patients central pathology review was performed. RESULTS: The 10-year cumulative risk of local breast cancer relapse as a first event was not significantly influenced if the margin was scored negative, close or positive for invasive tumor or ductal carcinoma in situ according to central pathology review (log-rank P = .45 and P = .57, respectively). In multivariate analysis, high-grade invasive ductal carcinoma was associated with an increased risk of local relapse (P = .026; hazard ratio [HR], 1.67), as was age younger than 50 years (P < .0001; HR, 2.38). The boost dose of 16 Gy significantly reduced the local relapse rate (P = .0006; HR, 0.47). For patients younger than 50 years old and in patients with high grade invasive ductal carcinoma, the boost dose reduced the local relapse from 19.4% to 11.4% (P = .0046; HR, 0.51) and from 18.9% to 8.6% (P = .01; HR, 0.42), respectively. CONCLUSION: Young age and high-grade invasive ductal cancer were the most important risk factors for local relapse, while margin status had no significant influence. A boost dose of 16 Gy significantly reduced the negative effects of both young age and high-grade invasive cancer