Preoperative MRI of the breast and ipsilateral breast tumor recurrence: Long-term follow up.

BACKGROUND: Local recurrence after breast conserving surgery is reported in 5-10% of cases. This study aims to determine if preoperative MRI is associated with reduced IBTR rates in the longer term and evaluate IBTR rates of a high risk (TN and Her-2 positive) subgroup in those receiving MRI or not. METHODS: Between 1999 and 2005, patients with invasive breast cancer undergoing BCS and radiation were identified. Primary endpoint was IBTR rate. RESULTS: The cohort consisted of 470 cases: 27% underwent MRI and 73% did not. Median follow-up was 97 months. Overall 10-year IBTR rate was 3.6%. There was no significant difference in IBTR rate at 10 years between those receiving MRI or not (1.6% vs. 4.2% (P = 0.37). The TN and Her-2 positive combined subgroup had a higher IBTR rate than all others (9.8% vs. 1.7%, P = 0.001). In the group without MRI, the IBTR rate of the high risk group was 11.8% compared to 1.8% in the remainder (P = 0.002). CONCLUSION: With 10-year follow-up, there was no significant difference in IBTR rate whether preoperative MRI is performed versus not. The high risk population showed an increased IBTR rate, this was more marked in those who did not receive MRI.

Post-mastectomy Radiation: Should Subtype Factor into the Decision?

BACKGROUND: Traditional indications do not factor molecular subtype into the decision making for post-mastectomy radiation (PMRT). We sought to determine whether constructed subtype was associated with receipt of PMRT in an academic cancer center and to assess differences in locoregional recurrence (LRR) by constructed subtype. METHODS: Patients treated with mastectomy as the primary surgical therapy were identified. Univariate and stepwise multivariate logistic regression analyses examined the association between covariates and PMRT. Kaplan-Meier estimates for the time to either the earlier of LRR or last follow-up were obtained for each subtype, and Cox proportional hazards regression examined the effect of covariates on time to LRR in both univariate analyses and stepwise multivariate analysis. RESULTS: Overall, 884 patients with invasive breast cancer who underwent a primary mastectomy between January 2002 and May 2012 were included in the study. A total of 359 patients (41.6 %) received PMRT. Compared with other subtypes, triple negative (TN; HR-/HER2-) cancers were more likely to be smaller (95 % T1/T2; p = 0.02) and have a lower nodal burden (N0 65 %; p < 0.0001). On multivariate analysis, age < 50 years, lymphovascular invasion (LVI), T stage, N stage, and close or positive margins remained significantly associated with PMRT, while constructed subtype was not associated with PMRT. Compared with all other subtypes, TN had the highest rate of LRR [hazard ratio (HR) 5.70; p < 0.0001]. On multivariable analysis, TN status, LVI, and not receiving chemotherapy were significantly associated with LRR. CONCLUSIONS: Despite significant differences in LRR by constructed subtype, receptor status does not appear to be associated with the receipt of PMRT. In our series, TN cancers had the highest risk of LRR despite their relatively smaller size and limited nodal disease.

Magnetic resonance imaging in the planning of initial lumpectomy for invasive breast carcinoma: its effect on ipsilateral breast tumor recurrence after breast-conservation therapy.

BACKGROUND: It remains uncertain whether routine preoperative breast magnetic resonance imaging (MRI) will lead to improved local outcomes after breast-conserving surgery (BCS) and radiation (RT) for invasive carcinoma. The purpose of this study was to determine whether MRI in the planning of the first lumpectomy reduces ipsilateral breast tumor recurrence (IBTR). METHODS: Using a prospective database, 472 initial lumpectomies from 463 women between 1999 and 2005 were examined. All patients had invasive cancer excised to negative margins on BCS, received RT, and were followed. IBTR rates were calculated by Kaplan-Meier method. Univariate and multivariate analyses were performed to investigate the association between MRI for initial lumpectomies and IBTR outcomes. RESULTS: MRI was performed before 127 (27%) lumpectomies, while 345 (73%) patients did not have a preoperative breast MRI. At median follow-up of 54 months (range 4.8-111.6 months), there was no significant difference in actuarial 8-year IBTR rates between women with preoperative MRI evaluation and women without MRI (1.8% versus 2.5%, respectively; P=0.67). After adjusting for adjuvant therapies, patient, and tumor characteristics, there continued to be no increased risk of IBTR [hazard ratio (HR) 1.7; P=0.60]. MRI visualization of tumors prior to lumpectomy did not influence the achievement of negative margins and was not associated with lower rates of re-excision (MRI: 11.8% versus no-MRI: 13.3%; P=0.50). CONCLUSION: MRI evaluation of invasive carcinoma in the planning of initial lumpectomies was not associated with improved local outcomes after BCS with RT in this cohort of patients.

Identification of dysphagia using the Toronto Bedside Swallowing Screening Test (TOR-BSST©): are 10 teaspoons of water necessary?

Dysphagia screening often includes administration of water. This study assessed the accuracy in identifying dysphagia with each additional teaspoon of water. The original research of the TOR-BSST(©) permitted this assessment. Trained nurses from acute and rehabilitation facilities prospectively administered the TOR-BSST(©) to 311 eligible stroke inpatients. A sensitivity analysis was conducted for the water item using 10 teaspoons plus a sip as the standard. The proportion of positive screenings was 59.2% in acute and 38.5% in rehabilitation. Of all four items that form the TOR-BSST(©), the water swallow item contributed to the identification of dysphagia in 42.7% in acute and 29.0% in rehabilitation patients. Across all patients, dysphagia accuracy was that five teaspoons resulted in a sensitivity of 79% (95% confidence interval [CI] = 70-86), eight a sensitivity of 92% (95% CI = 85-96) and 10 a sensitivity of 96% (95% CI = 90-99). Although a primary contributor, the water swallow item alone does not identify all patients with dysphagia. For a water swallow to accurately identify dysphagia, it is critical to administer 10 teaspoons. The TOR-BSST(©) water swallow item contributes largely to the total TOR-BSST(©)'s screening score and in making the test highly accurate and reliable.

Validation of an automated algorithm for detecting apneas and hypopneas by acoustic analysis of breath sounds.

BACKGROUND: Sleep-disordered breathing (SDB) is common and is associated with increased risk for cardiovascular disease. However, most patients remain undiagnosed due to lack of access to sleep laboratories. We therefore tested the validity of a single-channel monitoring setup that captures and analyzes breath sounds (BSs) to detect SDB. METHODS: BS were recorded from 50 patients undergoing simultaneous polysomnography (PSG). Using custom-designed automatic software, BS were subjected to a set of pattern recognition rules to identify apneas and hypopneas from which the acoustic apnea-hypopnea index (AHI-a) was calculated. Apneas and hypopneas from PSG were scored blindly by three technicians according to two criteria; one relying solely on the drop of the respiratory signal by >90% for an apnea and by 50% to 90% for a hypopnea (TV50 criteria), and another that also required a desaturation or an arousal for a hypopnea (American Association of Sleep Medicine [AASM] criteria). PSG AHI (AHI-p) was calculated for each technician according to both criteria. RESULTS: There was no significant difference between AHI-p scores according to TV50 and AASM criteria. AHI-a was strongly correlated with AHI-p according to both TV50 (R=94%) and AASM criteria (R=93%). Bland-Altman plot analysis revealed that 98% and 92% of AHI-a fell within the limits of agreement for AHI-p according to TV50 and AASM criteria, respectively. Based on a diagnostic cutoff of AHI-p≥10 for SDB, overall accuracy of AHI-a reached 88% and negative predictive value reached 100%. CONCLUSION: Acoustic analysis of BS is a reliable method for quantifying AHI and diagnosing SDB compared to simultaneous PSG.

Time courses of improvement and symptom remission in children treated with atomoxetine for attention-deficit/hyperactivity disorder: analysis of Canadian open-label studies.

BACKGROUND: The relatively short durations of the initial pivotal randomized placebo-controlled trials involving atomoxetine HCl for the treatment of attention-deficit/hyperactivity disorder (ADHD) provided limited insight into the time courses of ADHD core symptom responses to this nonstimulant, selective norepinephrine reuptake inhibitor. The aim of this analysis was to evaluate time courses of treatment responses or remission, as assessed by attainment of prespecified scores on the ADHD Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-PI) and the Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) scales, during up to 1 year of atomoxetine treatment in children with ADHD. METHODS: Using pooled data from three Canadian open-label studies involving 338 children ages 6-11 years with ADHD who were treated with atomoxetine for 3, 6 and 12 months, and survival analysis methods for interval-censored data, we estimated the time to: 1) improvement and robust improvement defined by ≥25% and ≥40% reductions from baseline ADHDRS-IV-PI total scores, respectively; and 2) remission using two definitions: a final score of ADHDRS-IV-PI ≤18 or a final score of CGI-ADHD-S ≤2. RESULTS: The median time to improvement was 3.7 weeks (~1 month), but remission of symptoms did not occur until a median of 14.3 weeks (~3.5 months) using the most stringent CGI-ADHD-S threshold. Probabilities of robust improvement were 47% at or before 4 weeks of treatment; 76% at 12 weeks; 85% at 26 weeks; and 96% at 52 weeks. Probabilities of remission at these corresponding time points were 30%, 59%, 77%, and 85% (using the ADHDRS-IV scale) and 8%, 47%, 67%, and 75% (using the CGI-ADHD-S scale). The change from atomoxetine treatment month 5 to month 12 of -1.01 (1.03) was not statistically significant (p = .33). CONCLUSIONS: Reductions in core ADHD symptoms during atomoxetine treatment are gradual. Although approximately one-half of study participants showed improvement at 1 month of atomoxetine treatment, remission criteria were not met until about 3 months. Understanding the time course of children's responses to atomoxetine treatment may inform clinical decision making and also influence the durations of trials comparing the effects of this medication with other ADHD treatments. TRIAL REGISTRATIONS: clinicaltrials.gov: NCT00191633, NCT00216918, NCT00191880.

Power and sample size considerations in clinical trials with competing risk endpoints.

In clinical trials with a time-to-event endpoint, subjects are often at risk for events other than the one of interest. When the occurrence of one type of event precludes observation of any later events or alters the probably of subsequent events, the situation is one of competing risks. During the planning stage of a clinical trial with competing risks, it is important to take all possible events into account. This paper gives expressions for the power and sample size for competing risks based on a flexible parametric Weibull model. Nonuniform accrual to the study is considered and an allocation ratio other than one may be used. Results are also provided for the case where two or more of the competing risks are of primary interest.