Long-term effects of cranial irradiation and intrathecal chemotherapy in treatment of childhood leukemia: a MEG study of power spectrum and correlated cognitive dysfunction

<p>Abstract</p> <p>Background</p> <p>Prophylaxis to prevent relapses in the central nervous system after childhood acute lymphoblastic leukemia (ALL) used to consist of both intrathecal chemotherapy (CT) and cranial irradiation (CRT). CRT was mostly abolished in the eighties because of its neurotoxicity, and replaced with more intensive intrathecal CT. In this study, a group of survivors treated with CRT before 1983 and another group treated without CRT thereafter are investigated 20–25 years later, giving a much stronger perspective on long-term quality of life than previous studies. The outcomes will help to better understand these groups’ current needs and will aid in anticipating late effects of prophylactic CRT that is currently applied for other diseases. This study evaluates oscillatory neuronal activity in these long-term survivors. Power spectrum deviations are hypothesized to correlate with cognitive dysfunction.</p> <p>Methods</p> <p>Resting state eyes-closed magnetoencephalography (MEG) recordings were obtained from 14 ALL survivors treated with CT + CRT, 18 treated with CT alone and 35 controls. Relative spectral power was calculated in the δ, θ, α1, α2, β and γ frequency bands. The Amsterdam Neuropsychological Tasks (ANT) program was used to assess cognition in the executive functions domain. MEG data and ANT scores were correlated.</p> <p>Results</p> <p>In the CT + CRT group, relative θ power was slightly increased (p = 0.069) and α2 power was significantly decreased (p = 0.006). The CT + CRT group performed worse on various cognitive tests. A deficiency in visuomotor accuracy, especially of the right hand, could be clearly associated with the deviating regional θ and α2 powers (0.471 < r < 0.697). A significant association between decreased regional α2 power and less attentional fluctuations was found for CT + CRT patients as well as controls (0.078 < r < 0.666). Patients treated with CT alone displayed a power spectrum similar to controls, except for a significantly increased level of left frontal α2 power (p = 0.030).</p> <p>Conclusions</p> <p>The tendency towards global slowing of brain oscillatory activity, together with the fact that dementia has been reported as a late effect of CRT and the neuropsychological deficiencies currently present, suggest that the irradiated brain might be aging faster and could be at risk for early‐onset dementia. The CT group showed no signs of early aging.</p

Low-Threshold-For-Surgery Versus Primarily-Conservative Treatment for Odontoid Fractures in the Elderly:Evaluating Practice Variation in The Netherlands

Study Design Retrospective cohort study. Objectives Odontoid fractures are the most common cervical spine fractures in the elderly. The optimal treatment remains controversial. The aim of this study was to compare results of a low-threshold-for-surgery strategy (surgery for dislocated fractures in relatively healthy patients) to a primarily-conservative strategy (for all patients). Methods Patient records from 5 medical centers were reviewed for patients who met the selection criteria (e.g. age &amp; GE;55 years, type II/III odontoid fractures). Demographics, fracture types/characteristics, fracture union/stability, clinical outcome and mortality were compared. The influence of age on outcome was studied (&amp; GE;55-80 vs &amp; GE;80 years). Results A total of 173 patients were included: 120 treated with low-threshold-for-surgery (of which 22 primarily operated, and 23 secondarily) vs 53 treated primarily-conservative. No differences in demographics and fracture characteristics between the groups were identified. Fracture union (53% vs 43%) and fracture stability (90% vs 85%) at last follow-up did not differ between groups. The majority of patients (56%) achieved clinical improvement compared to baseline. Analysis of differences in clinical outcome between groups was infeasible due to data limitations. In both strategies, patients &amp; GE;80 years achieved worse union (64% vs 30%), worse stability (97% vs 77%), and - as to be expected - increased mortality &lt;104 weeks (2% vs 22%). Conclusions Union and stability rates did not differ between the treatment strategies. Advanced age (&amp; GE;80 years) negatively influenced both radiological outcome and mortality. No cases of secondary neurological deficits were identified, suggesting that concerns for the consequences of under-treatment may be unjustified

Guideline adherence of mediastinal staging of non-small cell lung cancer:A multicentre retrospective analysis

Objectives: Mediastinal lymph node staging of NSCLC by initial endosonography and confirmatory mediastinoscopy is recommended by the European guideline. We assessed guideline adherence on mediastinal staging, whether staging procedures were performed systematically and unforeseen N2 rates following staging by endosonography with or without confirmatory mediastinoscopy. Material and Methods: We performed a multicentre (n = 6) retrospective analysis of NSCLC patients without distant metastases, who were surgical candidates and had an indication for mediastinal staging in the year 2015. All patients who underwent EBUS, EUS and/or mediastinoscopy were included. Surgical lymph node dissection was the reference standard. Guideline adherence was based on the 2014 ESTS guideline. Results: 330 consecutive patients (mean age 69 years; 61% male) were included. The overall prevalence of N2/N3 disease was 42%. Initial mediastinal staging by endosonography was done in 84% (277/330; range among centres 71-100%; p <.01). Confirmatory mediastinoscopy was performed in 40% of patients with tumour negative endosonography (61/154; range among centres 10%-73%; p <.01). Endosonography procedures were performed ‘systematically’ in 21% of patients (57/277) with significant variability among centres (range 0-56%; p <.01). Unforeseen N2 rates after lobe-specific lymph node dissection were 8.6% (3/35; 95%-CI 3.0-22.4) after negative endosonography versus 7.5% (3/40; 95% CI 2.6-19.9) after negative endosonography and confirmatory mediastinoscopy. Conclusion: Although adherence to the European NSCLC mediastinal staging guideline on initial use of endosonography was good, 30% of endosonography procedures were performed insufficiently. Confirmatory mediastinoscopy following negative endosonography was frequently omitted. Significant variability was found among participating centres regarding staging strategy and systematic performance of procedures. However, unforeseen N2 rates after mediastinal staging by endosonography with and without confirmatory mediastinoscopy were comparable