Local Failure and Survival After Definitive Radiotherapy for Aggressive Prostate Cancer: An Individual Patient-level Meta-analysis of Six Randomized Trials

BackgroundThe importance of local failure (LF) after treatment of high-grade prostate cancer (PCa) with definitive radiotherapy (RT) remains unknown.ObjectiveTo evaluate the clinical implications of LF after definitive RT.Design, setting, and participantsIndividual patient data meta-analysis of 992 patients (593 Gleason grade group [GG] 4 and 399 GG 5) enrolled in six randomized clinical trials.Outcome measurements and statistical analysisMultivariable Cox proportional hazard models were developed to evaluate the relationship between overall survival (OS), PCa-specific survival (PCSS), and distant metastasis (DM)-free survival (DMFS) and LF as a time-dependent covariate. Markov proportional hazard models were developed to evaluate the impact of specific transitions between disease states on these endpoints.Results and limitationsMedian follow-up was 6.4 yr overall and 7.2 yr for surviving patients. LF was significantly associated with OS (hazard ratio [HR] 1.70 [95% confidence interval {CI} 1.37–2.10]), PCSS (3.10 [95% CI 2.33–4.12]), and DMFS (HR 1.92 [95% CI 1.54–2.39]), p < 0.001 for all). Patients who had not transitioned to the LF state had a significantly lower hazard of transitioning to a PCa-specific death state than those who transitioned to the LF state (HR 0.13 [95% CI 0.04–0.41], p < 0.001). Additionally, patients who transitioned to the LF state had a greater hazard of DM or death (HR 2.46 [95% CI 1.22–4.93], p = 0.01) than those who did not.ConclusionsLF is an independent prognosticator of OS, PCSS, and DMFS in high-grade localized PCa and a subset of DM events that are anteceded by LF events. LF events warrant consideration for intervention, potentially suggesting a rationale for upfront treatment intensification. However, whether these findings apply to all men or just those without significant comorbidity remains to be determined.Patient summaryMen who experience a local recurrence of high-grade prostate cancer after receiving upfront radiation therapy are at significantly increased risks of developing metastases and dying of prostate cancer.     

The Added Value of Percentage of Free to Total Prostate-specific Antigen,PCA3, and a Kallikrein Panel to the ERSPC Risk Calculator for Prostate Cancer in Prescreened Men

Background

Prostate-specific antigen (PSA) testing has limited accuracy for the early detection of prostate cancer (PCa).

Objective

To assess the value added by percentage of free to total PSA (%fPSA), prostate cancer antigen 3 (PCA3), and a kallikrein panel (4k-panel) to the European Randomised Study of Screening for Prostate Cancer (ERSPC) multivariable prediction models: risk calculator (RC) 4, including transrectal ultrasound, and RC 4 plus digital rectal examination (4+DRE) for prescreened men.

Design, setting, and participants

Participants were invited for rescreening between October 2007 and February 2009 within the Dutch part of the ERSPC study. Biopsies were taken in men with a PSA level ≥3.0 ng/ml or a PCA3 score ≥10. Additional analyses of the 4k-panel were done on serum samples.

Outcome measurements and statistical analysis

Outcome was defined as PCa detectable by sextant biopsy. Receiver operating characteristic curve and decision curve analyses were performed to compare the predictive capabilities of %fPSA, PCA3, 4k-panel, the ERSPC RCs, and their combinations in logistic regression models.

Results and limitations

PCa was detected in 119 of 708 men. The %fPSA did not perform better univariately or added to the RCs compared with the RCs alone. In 202 men with an elevated PSA, the 4k-panel discriminated better than PCA3 when modelled univariately (area under the curve [AUC]: 0.78 vs 0.62; p = 0.01). The multivariable models with PCA3 or the 4k-panel were equivalent (AUC: 0.80 for RC 4+DRE). In the total population, PCA3 discriminated better than the 4k-panel (univariate AUC: 0.63 vs 0.56; p = 0.05). There was no statistically significant difference between the multivariable model with PCA3 (AUC: 0.73) versus the model with the 4k-panel (AUC: 0.71; p = 0.18). The multivariable model with PCA3 performed better than the reference model (0.73 vs 0.70; p = 0.02). Decision curves confirmed these patterns, although numbers were small.

Conclusions

Both PCA3 and, to a lesser extent, a 4k-panel have added value to the DRE-based ERSPC RC in detecting PCa in prescreened men.

Patient summary

We studied the added value of novel biomarkers to previously developed risk prediction models for prostate cancer. We found that inclusion of these biomarkers resulted in an increase in predictive ability.     

Female reproductive factors,menopausal hormone use,and Parkinson's disease

The objective of this study was to examine the associations of reproductive factors and exogenous hormone use with risk of Parkinson's disease (PD) among postmenopausal women. The study comprised 119,166 postmenopausal women aged 50 to 71 years in the NIH‐AARP Diet and Health Study, who completed a baseline questionnaire in 1995–1996 and a follow‐up survey in 2004–2006. A total of 410 self‐reported PD diagnoses were identified between 1995 and 2006. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic regression models. PD risk was not significantly associated with female reproductive factors including age at menarche, age at first live birth, parity, and age at menopause. For example, compared with women with natural menopause at age 50 to 54 years, the ORs were 1.18, (95% CI, 0.78‐1.79) for women with natural menopause aged <45, 1.19 (95% CI, 0.88‐1.61) for those aged 45 to 49, and 1.33 (95% CI, 0.91‐1.93) for those aged 55 or older. We found that oral contraceptive use for ≥10 years (vs. never used) was associated with lower PD risk (OR, 0.59; 95% CI, 0.38‐0.92), but shorter use showed no association. Use of menopausal hormone therapy showed inconsistent results. Compared with non–hormone users at baseline, current hormone users for <5 years showed a higher risk of PD (OR, 1.52; 95% CI, 1.11‐2.08). However, no associations were observed for past hormone users or current users of ≥5 years. Overall, this large prospective study provides little support for an association between female reproductive factors and PD risk. Our findings on long‐term oral contraceptive use and current hormone therapy warrant further investigations. © 2013 International Parkinson and Movement Disorder Society     

Factors Associated With Severe Uncontrolled Asthma and the Perception of Control by Physicians and Patients

IntroductionDespite current treatments, more than half of patients with asthma are not controlled. The objective was to evaluate the correlation between control perceived by patients and physicians, compared with control evaluated according to criteria of the Spanish Guidelines for Asthma Management (GEMA), and to investigate the factors associated with that control.MethodsMulticenter, cross-sectional, observational study including 343 patients with severe persistent asthma according to GEMA criteria seen in the Department of Pulmonology and Allergology. The correlation between asthma control perceived by the patient, the physician and according to clinical judgment based on the GEMA criteria was calculated, and a multivariate analysis was used to determine variables related to the perception of asthma control.ResultsAccording to GEMA criteria, only 10.2% of patients were well controlled, 27.7% had partial control and 62.1% were poorly controlled. Both the physicians and the patients overestimated control: 75.8% and 59.3% of patients had controlled asthma according to the patient and the physician, respectively, and were not controlled according to GEMA (P<.0001). Patients with uncontrolled asthma according GEMA had higher body mass index (P=.006) and physical inactivity (P=.016). Factors associated with a perceived lack of control by both physicians and patients were: nocturnal awakenings (≥1 day/week), frequent use of rescue medication (≥5 days/week) and significant limitation in activities. Discrepant factors between physicians and patients were dyspnea and emergency room visits (patients only), FEV1≤80% and a poorer understanding of the disease by the patient (physicians only).ConclusionsOnly 10% of patients with severe asthma evaluated in this study are controlled according to GEMA criteria. Patients and physicians overestimate control and the overestimation by patients is greater. Physical inactivity and obesity are associated with a lack of control according to GEMA.     

Randomized controlled trial of alfacalcidol supplementation for the reduction of hypocalcemia after total thyroidectomy

BackgroundThe aim of this study was to evaluate the effect of perioperative alfacalcidol on postoperative hypocalcemia after total thyroidectomy.MethodsA total of 219 patients scheduled for total thyroidectomy were randomized into groups not receiving (group A) or receiving (group B) perioperative alfacalcidol. Postoperative hypocalcemia was compared between groups on postoperative day (POD) 1 and POD2. Patients with hypocalcemia (<2.00 mmol/L) received oral calcium supplementation. Calcium and vitamin D levels were measured at 5-week and 6-month follow-ups.ResultsThe incidence of symptomatic hypocalcemia was significantly lower in group A (P = .02), whereas similarly low levels of calcemia were observed in both groups on POD1 (37% and 30%, respectively; P = not significant) and persisted on POD2 (14% and 6%, respectively; P = not significant). Patients with severe hypocalcemia (<1.90 mmol/L) showed faster recovery in group A compared with group B (6% vs 1%, P = .04). At 5 weeks, calcium and vitamin D levels were similar between the groups. Six months after surgery, 4% (group A) versus 0% (group B) of subjects exhibited permanent hypoparathyroidism (P = .04).ConclusionsAlthough the treatment did not correct vitamin D deficiency, perioperative alfacalcidol uptake resulted in decreased transient hypocalcemia and related symptoms in patients undergoing total thyroidectomy.     

Exercise in the first week following concussion among collegiate athletes: Preliminary findings

ObjectivesOur purpose was to examine the association between exercise after concussion with symptom severity, postural control, and time to symptom-resolution.DesignLongitudinal cohort.MethodsCollegiate athletes (n = 72; age = 20.2 ± 1.3 years; 46% female) with concussion completed a symptom questionnaire at initial (0.6 ± 0.8 days post-injury) and follow-up (2.9 ± 1.4 days post-injury) evaluations, and a postural control assessment at follow-up. Participants were grouped into those who exercised in between the time of injury and the follow-up evaluation and those who did not. Decisions regarding post-concussion exercise were made by a sports medicine team consisting of a single team physician and athletic trainers.ResultsThirteen athletes were not included in the current study, resulting in an 85% response rate. Thirteen of the athletes who completed the study exercised between evaluations (18%). There was no symptom resolution time difference between groups (median = 13 [IQR = 7–18] days vs. 13 [7–23] days; p = 0.83). Symptom ratings were similar between groups at the acute post-injury assessment (median PCSS = 18.5 [7.5–26] vs. 17 [14–40]; p = 0.21), but a main effect of group after adjusting for time from injury to assessment indicated the exercise group reported lower symptom severity than the no exercise group across both assessments (p = 0.044). The dual-task gait speed of the exercise group was higher than the no exercise group (0.90 ± 0.15 vs. 0.78 ± 0.16 m/s; p = 0.02).ConclusionsAthletes who were recommended aerobic exercise after concussion did not have worse outcomes than those who were not. Exercise within the first week after concussion does not appear to be associated with detrimental clinical outcomes.     

Increasing Subspecialization of the National Radiologist Workforce

PurposeThe aim of this study was to assess recent trends in the generalist versus subspecialist composition of the national radiologist workforce.MethodsPracticing radiologists were identified using 2012 to 2017 CMS Physician and Other Supplier Public Use Files. Work relative value units associated with radiologists’ billed claims were mapped to subspecialties using the Neiman Imaging Types of Service to classify radiologists as subspecialists when exceeding a 50% work effort in a given subspecialty and as generalists otherwise. Additional practice characteristics were obtained from CMS Physician Compare. Chi-square statistics were computed.ResultsThe percentage of radiologists practicing as subspecialists increased from 37.1% in 2012 and 2013 to 38.8% in 2014, 41.0% in 2015, 43.9% in 2016, and 44.6% in 2017. By subspecialty, 2012 to 2017 workforce changes were as follows: breast, +3.7%; abdominal, +2.4%; neuroradiology, +1.8%; musculoskeletal, +0.8%; cardiothoracic, +0.2%; nuclear, −0.2%; and interventional, −1.2%. Increased subspecialization overall was consistently observed (P < .05) across cohorts defined by gender, years in practice, practice size, and academic status. The degree of increasing subspecialization was greatest for female (+12.1%) and earlier career (+10.2% for those in practice <10 years) radiologists and those in larger groups (+7.2% for ≥100 members). Subspecialization increased in 45 states, and state-level increased subspecialization correlated weakly with population density (r = +0.248).ConclusionsIn recent years, the national radiologist workforce has become increasingly subspecialized, particularly related to shifts toward breast imaging, abdominal imaging, and neuroradiology. Although growing subspecialization may advance more sophisticated imaging care, a diminishing supply of generalists could affect patient access and potentially separate radiologists across workforce sectors.