Citations

SummaryThe significance of serum lactate dehydrogenase (LDH) in light chain (AL) amyloidosis has not been previously explored. We studied 1019 newly diagnosed patients and correlated the elevation of LDH above the upper limit of normal (ULN) with disease characteristics and outcome. Four hundred and nine patients had an LDH above ULN, representing 40% of the study population. Patients with an elevated LDH were older, were less likely to be male and had more extensive organ involvement compared to patients with a normal LDH. Patients with high LDH had greater cardiac and renal dysfunction. Elevated LDH was an independent prognostic marker for overall survival and for death within 6 months of diagnosis, but this was restricted to patients not eligible for stem cell transplant. Serum LDH may act as a marker for organ damage and should be explored as a potential marker for tissue healing and organ recovery.

AbstractPrior studies have revealed that the presence of increasing number of polyclonal plasma cells (pPCs) in the bone marrow (BM) are associated with better outcomes in newly diagnosed multiple myeloma (MM) patients. This effect has not been studied in patients with MM at the time of disease relapse. We determined the prognostic value of depletion of pPCs in the BM by 7‐color multiparameter flow cytometry in a series of 174 relapsing MM patients. The time to next therapy (TTNT) in those with <5% pPCs was 9.4 months versus 13.9 months in those with ≥5% pPCs (P = .0091). The median overall survival (OS) in those with <5% pPCs was 21.4 months, while the median OS was not reached in those patients with ≥5% pPCs (P = .019). Of the 109 patients with standard risk cytogenetics, the median OS of those with <5% pPCs was 28.4 months, while the median OS was not reached in those with ≥5% pPCs (P = .033). As such, <5% pPCs in the BM appears to have prognostic utility in identifying a subset of relapsing MM patients, even with standard‐risk cytogenetics, who have a particularly adverse outcome.

Abstract BACKGROUND There are conflicting data between natural history studies suggesting a very low risk of rupture for small, unruptured intracranial aneurysms and retrospective studies that have identified a much higher frequency of small, ruptured aneurysms than expected. OBJECTIVE To use the prospective International Study of Unruptured Intracranial Aneurysms cohort to identify morphological characteristics predictive of unruptured intracranial aneurysm rupture. METHODS A case-control design was used to analyze morphological characteristics associated with aneurysm rupture in the International Study of Unruptured Intracranial Aneurysms database. Fifty-seven patients with ruptured aneurysms during follow-up were matched (by size and location) with 198 patients with unruptured intracranial aneurysms without rupture during follow-up. Twelve morphological metrics were measured from cerebral angiograms in a blinded fashion. RESULTS Perpendicular height ( P = .008) and size ratio (ratio of maximum diameter to the parent vessel diameter; P = .01) were predictors of aneurysm rupture on univariate analysis. Aspect ratio, daughter sacs, multiple lobes, aneurysm angle, neck diameter, parent vessel diameter, and calculated aneurysm volume were not statistically significant predictors of rupture. On multivariate analysis, perpendicular height was the only significant predictor of rupture (Chi-square 7.1, P -value .008). CONCLUSION This study underscores the importance of other morphological factors, such as perpendicular height and size ratio, that may influence unruptured intracranial aneurysm rupture risk in addition to greatest diameter and anterior vs posterior location.

Abstract BACKGROUND One study has investigated postoperative growth rates following subtotal resection of petroclival meningiomas utilizing linear measurements, which are insensitive to the multidimensional complex growth of meningiomas, to estimate tumor volume. OBJECTIVE To describe petroclival meningioma growth patterns following less-than-complete resection utilizing volumetric analysis and to identify variables associated with tumor progression. METHODS Patients with surgically resected WHO grade I petroclival meningiomas were retrospectively reviewed (1999-2015). Image analysis software was utilized to perform volumetric analyses of tumor size and growth on serial MRI studies. The impact of preoperative and postoperative variables on tumor growth after subtotal resection was analyzed. An increase in tumor volume of at least 20% was defined as “tumor growth.” RESULTS Twenty-three patients had immediate preoperative and serial postoperative MRI studies available for review. The mean preoperative tumor volume was 20.9 cm 3 (range 0.4-54.6). The mean extent of resection was 75.5% (range 31.5%-100.0%). At a mean follow-up of 24.8 mo, 12 tumors (66.7%) exhibited radiological tumor growth, while 6 tumors did not change in size. The median annual volumetric growth rate was 2.82 cm 3 /yr (range –0.34 to 10.1). Extent of resection and immediate postoperative tumor volume were significantly correlated with the annual volumetric growth rate following resection. At last follow-up, 3 (13%) patients required further intervention. CONCLUSION The majority of petroclival meningiomas exhibit growth following subtotal resection. Extent of resection is strongly associated with risk for disease progression following surgery.

Abstract Background Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare malignant neoplasm of the olfactory mucosa. Despite surgical resection combined with radiotherapy and adjuvant chemotherapy, ENB often relapses with rapid progression. Current multimodality, nontargeted therapy for relapsed ENB is of limited clinical benefit. Materials and Methods We queried whether comprehensive genomic profiling (CGP) of relapsed or refractory ENB can uncover genomic alterations (GA) that could identify potential targeted therapies for these patients. CGP was performed on formalin-fixed, paraffin-embedded sections from 41 consecutive clinical cases of ENBs using a hybrid-capture, adaptor ligation based next-generation sequencing assay to a mean coverage depth of 593X. The results were analyzed for base substitutions, insertions and deletions, select rearrangements, and copy number changes (amplifications and homozygous deletions). Results Clinically relevant GA (CRGA) were defined as GA linked to drugs on the market or under evaluation in clinical trials. A total of 28 ENBs harbored GA, with a mean of 1.5 GA per sample. Approximately half of the ENBs (21, 51%) featured at least one CRGA, with an average of 1 CRGA per sample. The most commonly altered gene was TP53 (17%), with GA in PIK3CA, NF1, CDKN2A, and CDKN2C occurring in 7% of samples. Conclusion We report comprehensive genomic profiles for 41 ENB tumors. CGP revealed potential new therapeutic targets, including targetable GA in the mTOR, CDK and growth factor signaling pathways, highlighting the clinical value of genomic profiling in ENB.

PurposeThe vast majority of body CT exams are performed with automatic exposure control (AEC), which adapts the mean tube current to the patient size and modulates the tube current either angularly, longitudinally or both. However, most radiation dose estimation tools are based on fixed tube current scans. Accurate estimates of patient dose from AEC scans require knowledge of the tube current values, which is usually unavailable. The purpose of this work was to develop and validate methods to accurately estimate the tube current values prescribed by one manufacturer's AEC system to enable accurate estimates of patient dose.MethodsMethods were developed that took into account available patient attenuation information, user selected image quality reference parameters and x‐ray system limits to estimate tube current values for patient scans. Methods consistent with AAPM Report 220 were developed that used patient attenuation data that were: (a) supplied by the manufacturer in the CT localizer radiograph and (b) based on a simulated CT localizer radiograph derived from image data. For comparison, actual tube current values were extracted from the projection data of each patient. Validation of each approach was based on data collected from 40 pediatric and adult patients who received clinically indicated chest (n = 20) and abdomen/pelvis (n = 20) scans on a 64 slice multidetector row CT (Sensation 64, Siemens Healthcare, Forchheim, Germany). For each patient dataset, the following were collected with Institutional Review Board (IRB) approval: (a) projection data containing actual tube current values at each projection view, (b) CT localizer radiograph (topogram) and (c) reconstructed image data. Tube current values were estimated based on the actual topogram (actual‐topo) as well as the simulated topogram based on image data (sim‐topo). Each of these was compared to the actual tube current values from the patient scan. In addition, to assess the accuracy of each method in estimating patient organ doses, Monte Carlo simulations were performed by creating voxelized models of each patient, identifying key organs and incorporating tube current values into the simulations to estimate dose to the lungs and breasts (females only) for chest scans and the liver, kidney, and spleen for abdomen/pelvis scans. Organ doses from simulations using the actual tube current values were compared to those using each of the estimated tube current values (actual‐topo and sim‐topo).ResultsWhen compared to the actual tube current values, the average error for tube current values estimated from the actual topogram (actual‐topo) and simulated topogram (sim‐topo) was 3.9% and 5.8% respectively. For Monte Carlo simulations of chest CT exams using the actual tube current values and estimated tube current values (based on the actual‐topo and sim‐topo methods), the average differences for lung and breast doses ranged from 3.4% to 6.6%. For abdomen/pelvis exams, the average differences for liver, kidney, and spleen doses ranged from 4.2% to 5.3%.ConclusionsStrong agreement between organ doses estimated using actual and estimated tube current values provides validation of both methods for estimating tube current values based on data provided in the topogram or simulated from image data.

AbstractBackgroundData on the effect of systemic immunoglobulin light chain amyloidosis (AL amyloidosis) on thyroid function are limited.ObjectiveTo assess the prevalence of hypothyroidism in AL amyloidosis patients and determine its predictors.Methods1142 newly diagnosed AL amyloidosis patients were grouped based on the thyroid‐stimulating hormone (TSH) measurement at diagnosis: hypothyroid group (TSH above upper normal reference; >5 mIU L−1; n = 217, 19% of study participants) and euthyroid group (n = 925, 81%). Predictors for hypothyroidism were assessed in a binary multivariate model. Survival between groups was compared using the log‐rank test and a multivariate analysis.ResultsPatients with hypothyroidism were older, more likely to present with renal and hepatic involvement and had a higher light chain burden compared to patients in the euthyroid group. Higher proteinuria in patients with renal involvement and lower albumin in patients with hepatic involvement were associated with hypothyroidism. In a binary logistic regression model, age ≥65 years, female sex, renal involvement, hepatic involvement, kappa light chain restriction and amiodarone use were independently associated with hypothyroidism. Ninety‐three per cent of patients in the hypothyroid group with free thyroxine measurement had normal values, consistent with subclinical hypothyroidism. Patients in the hypothyroid group had a shorter survival compared to patients in the euthyroid group (4‐year survival 36% vs 43%; P = 0.008), a difference that was maintained in a multivariate analysis.ConclusionA significant proportion of patients with AL amyloidosis present with hypothyroidism, predominantly subclinical, which carries a survival disadvantage. Routine assessment of TSH in these patients is warranted.