Journal Scan – This Month in Other Journals, December 2017

Raza SM, Gidley PW, Meis JM, Grosshans DR, Bell D, DeMonte F. Multimodality Treatment of Skull Base Chondrosarcomas: The Role of Histology Specific Treatment Protocols. Neurosurgery. 2017;81(3):520-530. doi:10.1093/neuros/nyx042.

The authors studied the impact of histological subtype/grade on progression-free survival (PFS) and the indications for surgery, radiation, and chemotherapy based on histology in 37 patients with skull base chondrosarcomas. Of the conventional histologic subtype, 23% were grade 1, 63% were grade 2, and 14% were grade 3. In addition to surgery, mesenchymal / dedifferentiated CSAs (18% of the cohort) underwent neoadjuvant chemotherapy and 48.6% of the overall cohort received adjuvant radiotherapy. Histological grade/subtype and treatment factors were assessed for impact on median PFS. Conventional subtype vs mesenchymal / dedifferentiated was positively associated with median PFS (166 vs 24 months). Increasing conventional grade inversely correlated with median PFS. Gross total resection positively impacted PFS in conventional CSAs (111.8 vs 42.9months) and mesenchymal / dedifferentiated CSAs (58.2 vs 1.0 month). Adjuvant radiotherapy significantly impacted PFS in conventional grades 2 and 3. They conclude that there is a potential need for histological subtype/grade specific treatment protocols. For conventional CSAs, surgery alone provides optimal results grade 1 CSAs, while resection with adjuvant radiotherapy yields the best outcome for grade 2 and 3 CSAs.

6 Figures and 5 Tables

Harteveld AA, van der Kolk AG, van der Worp HB, et al. Detecting Intracranial Vessel Wall Lesions With 7T-Magnetic Resonance Imaging. Stroke. 2017;48(9):2601-2604. doi:10.1161/STROKEAHA.117.017868.

Fifty subjects (25 patients and 25 matched healthy controls) underwent 7T-magnetic resonance imaging with an intracranial vessel wall sequence before and after contrast administration.  Consecutive patients (>18 years of age) presenting with ischemic stroke or transient ischemic attack in the posterior cerebral circulation, as well as age- and sex-matched volunteers without a history of cerebrovascular disease, were screened for inclusion. Healthy volunteers were recruited via advertisement. Two raters scored the presence and contrast enhancement of arterial wall lesions in individual segments of the circle of Willis and its primary branches. Total burden and distribution of vessel wall lesions and lesion characteristics (configuration, thickening pattern, and contrast enhancement) were compared both between and within both groups. The results show that based on overall vessel wall lesion burden, there are no significant differences between the groups. Regarding individual arterial segments, only vessel wall lesions in the posterior cerebral artery were more frequently observed in patients (18.0%) than in controls (5.4%). Many of these lesions showed enhancement, both in patients (48.9%) and in controls (43.5%; P=0.41). In patients, the proportion of enhancing lesions was higher in the posterior circulation (53.3%) than in the anterior circulation (20.6%). A large proportion of vessel wall lesions showed contrast enhancement in both groups. In patients, this proportion was higher for the posterior circulation compared with the anterior circulation. A recent systematic review concluded that magnetic resonance imaging–detected intracranial plaque enhancement is strongly associated with ipsilateral acute ischemic stroke. However, in the current study, asymptomatic controls also showed a large amount of enhancing vessel wall lesions.*  Therefore, apart from the association of contrast enhancement with (acute) ischemic stroke, vessel wall enhancement could also represent vasa vasorum neovascularization that may have developed as a result of normal vessel wall thickening during aging.

They conclude that while the overall intracranial vessel wall lesion burden and contrast enhancement were comparable between patients with recent posterior circulation ischemia and healthy controls, the study also revealed significant differences between the 2 groups, suggesting an association between posterior circulation lesion burden/enhancement and ischemic events.

3 Figures

*Gupta A, Baradaran H, Al-Dasuqi K, Knight-Greenfield A, Giambrone AE, Delgado D, et al. Gadolinium enhancement in intracranial atherosclerotic plaque and ischemic stroke: a systematic review and meta-analysis. J Am Heart Assoc. 2016;5:pii: e003816. doi: 10.1161/

JAHA.116.003816.

Thorén M, Azevedo E, Dawson J, et al. Predictors for Cerebral Edema in Acute Ischemic Stroke Treated With Intravenous Thrombolysis. Stroke. 2017;48(9):2464-2471. doi:10.1161/STROKEAHA.117.018223.

The authors aimed to determine which baseline clinical and radiological parameters predict development of cerebral edema in patients treated with intravenous thrombolysis. They used an image-based classification of cerebral edema with 3 degrees of severity (less severe CED 1 and most severe CED 3) on post intravenous thrombolysis imaging scans. They extracted data from 42,187 patients recorded in the SITS International Register (Safe Implementation of Treatments in Stroke) during 2002 to 2011. They performed univariate comparisons of baseline data between patients with or without cerebral edema.

Cerebral edema grade 1 was defined as focal edema up to one third of the hemisphere, cerebral edema 2 was focal edema greater than one third of the hemisphere, and CED grade 3 was edema with midline shift. While not explicitly mentioned in the study protocol, signs of focal edema usually are defined as narrowing of the cerebrospinal fluid space, for example, effacement of cortical sulci or ventricular compression.

They note the following limitations: First, the definition of edema is imaging-based, done mostly with CT, and not based on other clinical findings or tissue analysis. As with other similar definitions, they have no data on its sensitivity. Moreover, the edema classification they used is 2 decades old and needs a modification in the future, in combination with modern imaging and clinical data by prospective study. As a part of the ischemic process, early or mild edema may be difficult to distinguish from infarction.

They conclude that the most important baseline predictors for early CED are NIH Stroke Scale, hyperdense artery sign, higher blood glucose, decreased level of consciousness, and signs of infarct at baseline. The findings can be used to improve selection and monitoring of patients for drug or surgical treatment.

No surprises.

Trevisson E, Cassina M, Opocher E, et al. Natural history of optic pathway gliomas in a cohort of unselected patients affected by Neurofibromatosis 1. J Neurooncol. 2017;134(2):279-287. doi:10.1007/s11060-017-2517-6.

Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant conditions with an incidence of about 1:3500. It is caused by loss-of-function mutations of NF1, encoding neurofibromin that acts as a tumor suppressor by negatively regulating the GTPase activity of p21RAS and by controlling the serine threonine kinase MTOR. About 50% of patients carry a de novo mutation. Optic pathway glioma (OPG) in NF1 are classified according to their anatomical location: the pre-chiasmatic tracts of the optic nerves, the chiasmatic-hypothalamic region and/or the posterior optic pathways. Some studies have reported that posterior involvement of the optic pathway is associated with a worse visual outcome, however other studies have not confirmed this finding.

They assessed the natural history of optic pathway glioma in a cohort of unselected patients affected by NF1. They retrospectively evaluated 414 consecutive patients affected by NF1 and referred to their NF1 clinic before age 6. Average follow-up was 11.9 years: 52 out of 414 patients had optic pathway glioma with a total cumulative incidence of 15.4% at age 15.

The authors confirmed that about half of NF1 patients with optic pathway glioma presents clinical symptoms or signs at the diagnosis or during the follow-up, including mainly a decrease in visual acuity, ophthalmoscopy or OCT alterations and, in five patients, precocious puberty, which however, as previously observed, is not always associated with a hypothalamic involvement and it is not an indication to undertake chemotherapeutic treatment, even though it is often associated with obstructive hydrocephalus. They did not observe significant differences in the visual outcome, in the need for treatment nor in the tumor location between patients who underwent brain/orbit MRI for screening purposes or for specific clinical indications. Therefore, the present work further supports previous findings regarding the lack of indication of baseline MRI in children with NF1.

4 Tables

Fan AP, Guo J, Khalighi MM, et al. Long-Delay Arterial Spin Labeling Provides More Accurate Cerebral Blood Flow Measurements in Moyamoya Patients. Stroke. 2017;48(9):2441-2449. doi:10.1161/STROKEAHA.117.017773.

Among the most promising noninvasive techniques for perfusion imaging is arterial spin labeling (ASL) MRI that magnetically labels endogenous, flowing spins in feeding arteries to image CBF. ASL has demonstrated potential in numerous cerebrovascular and neurological disorders. However, typical ASL protocols fail in regions with long transit delays through collateral pathways, for example, in Moyamoya patients with abnormally long Tmax (time to-maximum of the residue function) on DSC. In these patients, if the prescribed post-labeling delay (PLD) is too short relative to the arrival time of tagged spins, ASL underestimates or fails to detect blood flow through collateral vasculature. For ASL to accurately measure CBF in Moyamoya disease or other steno-occlusive disorders, more sophisticated acquisitions are necessary.

The authors compared standard-delay ASL (post-label delay=2.025 seconds), multidelay ASL (post-label delay=0.7–3.0 seconds), and long-label long-delay ASL acquisitions (post-label delay=4.0 seconds) against simultaneous [15O]-PET CBF maps in 15 Moyamoya patients on a hybrid PET/MRI scanner. Dynamic susceptibility contrast was performed in each patient to identify areas of mild, moderate, and severe time-to-maximum (Tmax) delays. Relative CBF measurements by each ASL scan in 20 cortical regions were compared with the PET reference standard, and correlations were calculated for areas with moderate and severe Tmax delays.

Standard-delay ASL underestimated relative CBF by 20% in areas of severe Tmax delays, particularly in anterior and middle territories commonly affected by Moyamoya disease. Arterial transit times correction by multidelay acquisitions led to improved consistency with PET, but still underestimated CBF in the presence of long transit delays. Long-label long-delay ASL scans showed the strongest correlation relative to PET, and there was no difference in mean relative CBF between the modalities, even in areas of severe delays.

They summarized the main conclusions as: 1. Standard-delay ASL acquisitions with post-labeling delay of 2 seconds led to dramatic underestimation of rCBF in anterior and middle cerebral artery perfusion territories with moderate and long transit delays in patients; 2. Multidelay ASL scans improved the correlation with PET through direct consideration of arterial transit time and a 2-compartment model but still resulted in noticeable rCBF underestimation for long transit delays; and 3. Long label long delay ASL acquisitions with label duration of 3 seconds and post label delay of 4 seconds, was comparable to Tmax delays measured by DSC, led to the strongest CBF correlation with PET scans in cases of long transit delays.

4 Figures , 2 tables

Uygunoglu U, Zeydan B, Ozguler Y, et al. Myelopathy in Behçet’s disease: The Bagel Sign. Ann Neurol. 2017;82(2):288-298. doi:10.1002/ana.25004.

BD is a chronic, multisystemic, vascular-inflammatory disease of unknown origin. According to the International Study Group (ISG) criteria, BD diagnosis requires recurrent oral aphthous ulcerations with two of the following: genital ulcerations, skin lesions, eye lesions, or a positive pathergy test. Neurological involvement, referred to as neuro-Behcet’s Syndrome (NBS), occurs in approximately 5% to 10% of all patients with BD. Two major forms of NBS are identified: cerebral venous sinus thrombosis and parenchymal NBS (p-NBS) (70–80% of all NBS).

The authors report on a cohort of 11 patients (9 men, 2 women), studied with 14 MRIs during distinct myelopathy episodes and nine follow-up MRIs. Two distinct MRI patterns of spinal cord involvement were described according to T2-weighted (T2W) axial images: (1) “Bagel Sign” pattern: a central lesion with hypointense core and hyperintense rim with or without contrast enhancement; and (2) “Motor Neuron” pattern: a symmetric involvement of the anterior horn cells. Bagel Sign was present in 13 of 14 myelopathy episodes whereas Motor Neuron pattern was observed in 1 of 14 MRIs.

5 Figures

Moreau P, Attal M, Caillot D, et al. Prospective Evaluation of Magnetic Resonance Imaging and [ 18 F]Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography at Diagnosis and Before Maintenance Therapy in Symptomatic Patients With Multiple Myeloma Included in the IFM/DFCI 2009 Trial. J Clin Oncol. 2017;35(25):2911-2918. doi:10.1200/JCO.2017.72.2975.

It has been previously shown in large series of patients treated with frontline autologous stem-cell transplantation (ASCT), that the number of focal lesions (FLs) evaluated by MRI at baseline was a strong predictor of event-free survival and that the number of FLs detected at baseline by FDG PET-CT retained a prognostic value for OS. In addition, the suppression of PET FLs at the time of the first transplantation was also a strong predictor of OS.  Nevertheless, few trials have prospectively compared MRI and PET-CT in the setting of frontline intensive therapy programs, including proteasome inhibitors and immunomodulatory drugs. The IFM/DFCI 2009 study prospectively evaluated the combination of eight cycles of lenalidomide, bortezomib, and dexamethasone (RVD) versus RVD plus autologous stem-cell transplantation, followed by lenalidomide maintenance. Within this clinical trial, a subgroup of patients was enrolled into the prospective ancillary study aimed at comparing MRI and FDG PET-CT at diagnosis after three cycles of RVD and before maintenance.

MRI images of the spine and pelvis were acquired using a whole-body MRI scanner. Standard protocol included T1-weighted turbo spin echo (TSE), STIR with fat suppression, and contrast-enhanced T1-weighted TSE with fat suppression.  Typical MM bone lesions at diagnosis appeared as hypointense T1-weighted TSE, hyperintense T2-weighted STIR, or hyperintense contrast T1-weighted TSE FLs. Other patterns included diffuse BM infiltration or a salt-and-pepper aspect with a heterogeneous BM signal resulting from multiple micronodules. Number and size of such FLs (considered if greater than or equal to 5 mm diameter) were registered.

MRI results were positive in 127 of 134 patients (95%), and PET-CT results were positive in 122 of 134 patients (91%). Normalization of MRI after three cycles of RVD and before maintenance was not predictive of PFS or OS. PET-CT became normal after three cycles of RVD in 32% of the patients with a positive evaluation at baseline, and PFS was improved in this group. PET-CT normalization before maintenance was described in 62% of the patients who were positive at baseline. This was associated with better PFS and OS. Extramedullary disease at diagnosis was an independent prognostic factor for PFS and OS, whereas PET-CT normalization before maintenance was an independent prognostic factor for PFS.

They conclude that there is no difference in the detection of bone lesions at diagnosis when comparing PET-CT and MRI. PET-CT is a powerful tool to evaluate the prognosis of de novo myeloma. They state that the study clearly shows a high detection rates of both imaging methods. They detect lesions in more than 90% of patients, without any clear superiority of one technique over the other.  Of note, they did not use entire-body MRI or diffusion-weighted imaging MRI, which may increase sensitivity. Nevertheless, their positivity rate of 95% demonstrates the value of performing MRI of the spine and pelvis in patients with symptomatic MM at diagnosis.

5 Figures which are PFS and OS graphs.  No MR images.

 

Ho AS, Kim S, Tighiouart M, et al. Metastatic Lymph Node Burden and Survival in Oral Cavity Cancer. J Clin Oncol. September 2017:JCO2016711176. doi:10.1200/JCO.2016.71.1176.

Regional neck metastasis represents an ominous prognostic factor in head and neck squamous cell carcinoma (HNSCC). The presence of just one metastatic lymph node (LN) commits patients to an advanced-stage disease category and has been shown to confer up to a 50% decrease in overall survival (OS). The American Joint Committee on Cancer (AJCC) staging system classically incorporates numerous factors to account for nodal disease, including size, laterality, and number of malignant nodes. Recent changes also factor in extranodal extension (ENE), also known as extracapsular spread.

Recent studies in mucosal head and neck cancers have suggested that the number of positive nodes or the number of nodes examined may convey a better measure of prognosis. Given the need for more precise staging metrics and treatment stratification, the authors investigated the impact of quantitative metastatic nodal burden in a large population of patients with oral cavity cancer (tongue, buccal mucosae and hard palate). They focused on oral cavity cancers because of their surgical treatment paradigm with more complete pathologic nodal data.

Overall, 14,554 patients met inclusion criteria (7,906 N0 patients; 6,648 node-positive patients). Mortality risk escalated continuously with increasing number of metastatic nodes without plateau, with the effect most pronounced with up to four LNs. Extranodal extension and lower neck involvement also predicted increased mortality. In multivariable models accounting for the number of metastatic nodes, contralateral LN involvement (N2c status) and LN size were not associated with mortality.

They conclude that they have demonstrated that the absolute number of metastatic LNs is a critical predictor of oral cavity cancer mortality, surpassing other nodal covariables, including size, contralaterality, extranodal extension, and lower neck involvement. Using a continuous multivariable regression model, they found that successive positive nodes increased the risk of death without plateau. Each positive LN conferred an added 34% increased risk of death through four positive nodes, whereas each successive positive node beyond this increased relative mortality by 3%.

4 Figures with Kaplan-Meier plots.

 

Journal Scan – This Month in Other Journals, December 2017
jross
Jeffrey Ross • Mayo Clinic, Phoenix

Dr. Jeffrey S. Ross is a Professor of Radiology at the Mayo Clinic College of Medicine, and practices neuroradiology at the Mayo Clinic in Phoenix, Arizona. His publications include over 100 peer-reviewed articles, nearly 60 non-refereed articles, 33 book chapters, and 10 books. He was an AJNR Senior Editor from 2006-2015, is a member of the editorial board for 3 other journals, and a manuscript reviewer for 10 journals. He became Editor-in-Chief of the AJNR in July 2015. He received the Gold Medal Award from the ASSR in 2013.

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