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Supplementary Methods. Supplementary Table S1: Baseline characteristics of PCNSL Patients. Supplementary Table S2: Baseline characteristics of SCNSL patients. Supplementary Table S3: Corticosteroid use. Supplementary Table S4: Genes with Recurrent Mutations in PCNSL (non-aSHM). Supplementary Table S5: Genes that are targeted by aSHM in PCNSL. Supplementary Table S6: Comparison of mutation prevalence in current PCNSL genomic landscape analysis (red) with prior studies in PCNSL and DLBCL. Supplementary Table S7: Gene set enrichment analysis of CD79B-mutant PCNSLs compared to CD79B-wildtype PCNSLs. Supplementary Figure S1: Ibrutinib concentrations in Cerebrospinal Fluid (CSF). Supplementary Figure S2: Comparison of mutation frequencies in PCNSL and DLBCL outside the CNS. Supplementary Figure S3: Cell-of-origin (COO) Markers in PCNSL. Supplementary Figure S4: CD79B-mutant PCNSL xenograft models. Supplementary Figure S5: Comparison of PCNSL cells with non-CNS DLBCL cell lines. Supplementary Figure S6: Inhibition of individual PI3K isoforms does not induce cell death in CD79B-mutant PCNSL cells. Supplementary Figure S7: In-vitro effects of ibrutinib on CD79B-mutant PCNSL cells.

The purpose of the present pilot study was to estimate T1 and T2 metric values derived simultaneously from a new, rapid Magnetic Resonance Fingerprinting (MRF) technique, as well as to assess their ability to characterize—brain metastases (BM) and normal-appearing brain tissues. Fourteen patients with BM underwent MRI, including prototype MRF, on a 3T scanner. In total, 108 measurements were analyzed: 42 from solid parts of BM’s (21 each on T1 and T2 maps) and 66 from normal-appearing brain tissue (11 ROIs each on T1 and T2 maps for gray matter [GM], white matter [WM], and cerebrospinal fluid [CSF]). The BM’s mean T1 and T2 values differed significantly from normal-appearing WM (p < 0.05). The mean T1 values from normal-appearing GM, WM, and CSF regions were 1205 ms, 840 ms, and 4233 ms, respectively. The mean T2 values were 108 ms, 78 ms, and 442 ms, respectively. The mean T1 and T2 values for untreated BM (n = 4) were 2035 ms and 168 ms, respectively. For treated BM (n = 17) the T1 and T2 values were 2163 ms and 141 ms, respectively. MRF technique appears to be a promising and rapid quantitative method for the characterization of free water content and tumor morphology in BMs.

The present exploratory study investigates the performance of a new, rapid, synthetic MRI method for diagnostic image quality assessment and measurement of relaxometry metric values in head and neck (HN) tumors and normal-appearing masseter muscle. The multi-dynamic multi-echo (MDME) sequence was used for data acquisition, followed by synthetic image reconstruction on a 3T MRI scanner for 14 patients (3 untreated and 11 treated). The MDME enables absolute quantification of physical tissue properties, including T1 and T2, with a shorter scan time than the current state-of-the-art methods used for relaxation measurements. The vendor termed the combined package MAGnetic resonance imaging Compilation (MAGiC). In total, 48 regions of interest (ROIs) were analyzed, drawn on normal-appearing masseter muscle and tumors in the HN region. Mean T1 and T2 values obtained from normal-appearing muscle were 880 ± 52 ms and 46 ± 3 ms, respectively. Mean T1 and T2 values obtained from tumors were 1930 ± 422 ms and 77 ± 13 ms, respectively, for the untreated group, 1745 ± 410 ms and 107 ± 61 ms, for the treated group. A total of 1552 images from both synthetic MRI and conventional clinical imaging were assessed by the radiologists to provide the rating for T1w and T2w image contrasts. The synthetically generated qualitative T2w images were acceptable and comparable to conventional diagnostic images (93% acceptability rating for both). The acceptability ratings for MAGiC-generated T1w, and conventional images were 64% and 100%, respectively. The benefit of MAGiC in HN imaging is twofold, providing relaxometry maps in a clinically feasible time and the ability to generate a different combination of contrast images in a single acquisition.

Current clinical and imaging tools remain suboptimal for predicting treatment response and prognosis in CNS lymphomas. We investigated the prognostic value of baseline [18F]FDG PET in patients with CNS lymphoma receiving ibrutinib-based treatments. Fifty-three patients enrolled in a prospective clinical trial and underwent brain PET before receiving single-agent ibrutinib or ibrutinib in combination with methotrexate with or without rituximab. [18F]FDG uptake in these lesions was quantified by drawing PET volumes of interest around up to five [18F]FDG-avid lesions per patient (with uptake greater than surrounding brain). We measured standardized uptake values (SUVmax), metabolic tumor volumes, total lesion glycolysis (TLG), and the sum thereof in these lesions. We analyzed the relationship between PET parameters and mutation status, overall response rates, and progression-free survival (PFS). Thirty-eight patients underwent single-agent therapy and 15 received combination therapy. On PET, 15/53 patients had no measurable disease. In the other 38 patients, a total of 71 lesions were identified on PET. High-intensity [18F]FDG uptake and a larger volume of [18F]FDG-avid disease were inversely related to treatment outcome (p ≤ 0.005). In univariable analysis, PFS was linearly correlated with all PET parameters, with stronger association when sum-values were used. A multivariable model showed that risk of progression increased by 9% for every 5-unit increase in sumSUVmax (hazard ratio = 1.09 [95% CI: 1.04 to 1.14]). Higher lesional metabolic parameters are inversely related to outcome in patients undergoing ibrutinib-based therapies, and sumSUVmax emerged as a strong independent prognostic factor. NCT02315326; https://clinicaltrials.gov/ct2/show/NCT02315326?term=NCT02315326&draw=2&rank=1

Cancer care increasingly relies on imaging for patient management. The two most common cross-sectional imaging modalities in oncology are computed tomography (CT) and magnetic resonance imaging (MRI), which provide high-resolution anatomic and physiological imaging. Herewith is a summary of recent applications of rapidly advancing artificial intelligence (AI) in CT and MRI oncological imaging that addresses the benefits and challenges of the resultant opportunities with examples. Major challenges remain, such as how best to integrate AI developments into clinical radiology practice, the vigorous assessment of quantitative CT and MR imaging data accuracy, and reliability for clinical utility and research integrity in oncology. Such challenges necessitate an evaluation of the robustness of imaging biomarkers to be included in AI developments, a culture of data sharing, and the cooperation of knowledgeable academics with vendor scientists and companies operating in radiology and oncology fields. Herein, we will illustrate a few challenges and solutions of these efforts using novel methods for synthesizing different contrast modality images, auto-segmentation, and image reconstruction with examples from lung CT as well as abdome, pelvis, and head and neck MRI. The imaging community must embrace the need for quantitative CT and MRI metrics beyond lesion size measurement. AI methods for the extraction and longitudinal tracking of imaging metrics from registered lesions and understanding the tumor environment will be invaluable for interpreting disease status and treatment efficacy. This is an exciting time to work together to move the imaging field forward with narrow AI-specific tasks. New AI developments using CT and MRI datasets will be used to improve the personalized management of cancer patients.

Background Patients with human papillomavirus–related oropharyngeal cancers have excellent outcomes but experience clinically significant toxicities when treated with standard chemoradiotherapy (70 Gy). We hypothesized that functional imaging could identify patients who could be safely deescalated to 30 Gy of radiotherapy. Methods In 19 patients, pre- and intratreatment dynamic fluorine-18-labeled fluoromisonidazole positron emission tomography (PET) was used to assess tumor hypoxia. Patients without hypoxia at baseline or intratreatment received 30 Gy; patients with persistent hypoxia received 70 Gy. Neck dissection was performed at 4 months in deescalated patients to assess pathologic response. Magnetic resonance imaging (weekly), circulating plasma cell-free DNA, RNA-sequencing, and whole-genome sequencing (WGS) were performed to identify potential molecular determinants of response. Samples from an independent prospective study were obtained to reproduce molecular findings. All statistical tests were 2-sided. Results Fifteen of 19 patients had no hypoxia on baseline PET or resolution on intratreatment PET and were deescalated to 30 Gy. Of these 15 patients, 11 had a pathologic complete response. Two-year locoregional control and overall survival were 94.4% (95% confidence interval = 84.4% to 100%) and 94.7% (95% confidence interval = 85.2% to 100%), respectively. No acute grade 3 radiation–related toxicities were observed. Microenvironmental features on serial imaging correlated better with pathologic response than tumor burden metrics or circulating plasma cell-free DNA. A WGS-based DNA repair defect was associated with response (P = .02) and was reproduced in an independent cohort (P = .03). Conclusions Deescalation of radiotherapy to 30 Gy on the basis of intratreatment hypoxia imaging was feasible, safe, and associated with minimal toxicity. A DNA repair defect identified by WGS was predictive of response. Intratherapy personalization of chemoradiotherapy may facilitate marked deescalation of radiotherapy.

BACKGROUND AND PURPOSE: Cognitive challenges are prevalent in survivors of glioma, but their neurobiology is incompletely understood. The purpose of this study was to investigate the effect of glioma presence and tumor characteristics on resting-state functional connectivity and amplitude of low-frequency fluctuations of the salience network, a key neural network associated with cognition. MATERIALS AND METHODS: Sixty-nine patients with glioma (mean age, 48.74 [SD, 14.32] years) who underwent resting-state fMRI were compared with 31 healthy controls (mean age, 49.68 [SD, 15.54] years). We identified 4 salience network ROIs: left/right dorsal anterior cingulate cortex and left/right anterior insula. Average salience network resting-state functional connectivity and amplitude of low-frequency fluctuations within the 4 salience network ROIs were computed. RESULTS: Patients with gliomas showed decreased overall salience network resting-state functional connectivity (P = .001) and increased amplitude of low-frequency fluctuations in all salience network ROIs (P

BACKGROUND AND PURPOSE: To determine the ability of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict long-term response of brain metastases prior to and within 72 hours of stereotactic radiosurgery (SRS). METHODS: In this prospective pilot study, multiple b-value DWI and T1-weighted DCE-MRI were performed in patients with brain metastases before and within 72 hours following SRS. Diffusion-weighted (DW) images were analyzed using the monoexponential and intravoxel incoherent motion (IVIM) models. DCE-MRI data were analyzed using the extended Tofts pharmacokinetic model. The parameters obtained with these methods were correlated with brain metastasis outcomes according to modified Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. RESULTS: We included 25 lesions from 16 patients; 16 patients underwent pre-SRS MRI and 12/16 patients underwent both pre- and early (within 72 hours) post-SRS MRI. The perfusion fraction (f) derived from IVIM early post-SRS was higher in lesions demonstrating progressive disease than in lesions demonstrating stable disease, partial response, or complete response (q = 0.041). Pre-SRS extracellular extravascular volume fraction, v(e), and volume transfer coefficient, k(trans), derived from DCE-MRI were higher in non-responders versus responders (q = 0.041). CONCLUSIONS: Quantitative DWI and DCE-MRI are feasible imaging methods in the pre- and early (within 72 hours) post-SRS evaluation of brain metastases. DWI- and DCE-MRI-derived parameters demonstrated physiologic changes (tumor cellularity and vascularity) and offer potentially useful biomarkers that can predict treatment response. This allows for initiation of alternate therapies within an effective time window that may help prevent disease progression.

The present preliminary study aims to characterize brain metastases (BM) using T1 and T2 maps generated from newer, rapid, synthetic MRI (MAGnetic resonance image Compilation; MAGiC) in a clinical setting. We acquired synthetic MRI data from 11 BM patients on a 3T scanner. A multiple-dynamic multiple-echo (MDME) sequence was used for data acquisition and synthetic image reconstruction, including post-processing. MDME is a multi-contrast sequence that enables absolute quantification of physical tissue properties, including T1 and T2, independent of the scanner settings. In total, 82 regions of interest (ROIs) were analyzed, which were obtained from both normal-appearing brain tissue and BM lesions. The mean values obtained from the 48 normal-appearing brain tissue regions and 34 ROIs of BM lesions (T1 and T2) were analyzed using standard statistical methods. The mean T1 and T2 values were 1143 ms and 78 ms, respectively, for normal-appearing gray matter, 701 ms and 64 ms for white matter, and 4206 ms and 390 ms for cerebrospinal fluid. For untreated BMs, the mean T1 and T2 values were 1868 ms and 100 ms, respectively, and 2211 ms and 114 ms for the treated group. The quantitative T1 and T2 values generated from synthetic MRI can characterize BM and normal-appearing brain tissues.

Objectives The aim of this study was to [1] characterize distribution of Erdheim-Chester Disease (ECD) by 18F-FDG PET/CT and [2] determine the utility of metabolic (18F-FDG PET/CT) imaging versus anatomic imaging (CT or MRI) in evaluating ECD patients for clinical trial eligibility. Methods 18F-FDG PET/CT and corresponding CT or MRI studies for ECD patients enrolled in a prospective registry study were reviewed. Sites of disease were classified as [1] detectable by 18F-FDG PET only, CT/MRI only, or both and as [2] measurable by modified PERCIST (mPERCIST) only, RECIST only, or both. Descriptive analysis was performed and paired t test for between-group comparisons. Results Fifty patients were included (mean age 51.5 years; range 18–70 years). Three hundred thirty-three disease sites were detected among all imaging modalities, 188 (56%) by both 18F-FDG PET and CT/MRI, 67 (20%) by 18F-FDG PET only, 75 (23%) by MRI brain only, and 3 (1%) by CT only. Of 178 disease sites measurable by mPERCIST or RECIST, 40 (22%) were measurable by both criteria, 136 (76%) by mPERCIST only, and 2 (1%) by RECIST only. On the patient level, 17 (34%) had mPERCIST and RECIST measurable disease, 30 (60%) had mPERCIST measurable disease only, and 0 had RECIST measurable disease only (p Conclusion Compared with anatomic imaging, 18F-FDG PET/CT augments evaluation of disease extent in ECD and increases identification of disease sites measurable by formal response criteria and therefore eligibility for clinical trials. Complementary organ-specific anatomic imaging offers the capacity to characterize sites of disease in greater anatomic detail. Trial registration ClinicalTrials.gov Identifier: NCT03329274

Human epidermal growth factor receptor 2 (HER2)-targeted zirconium 89–pertuzumab PET/CT successfully helped to identify HER2-positive metastases in women with HER2-negative primary breast cancer.

Invasive lobular carcinoma (ILC) demonstrates lower conspicuity on 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET than the more common invasive ductal carcinoma (IDC). Other molecular imaging methods may be needed for evaluation of this malignancy. As ILC is nearly always (95%) estrogen receptor (ER) positive, ER-targeting PET tracers such as 16α-[18F]-fluoroestradiol ([18F]FES) may have value. We reviewed prospective trials at Memorial Sloan Kettering Cancer Center (MSK) utilizing [18F]FES PET/CT to evaluate metastatic ILC patients with synchronous [18F]FDG and [18F]FES PET/CT imaging, which allowed a head-to-head comparison of these two PET tracers. Methods: Six prospective clinical trials utilizing [18F]FES PET/CT in patients with metastatic breast cancer were performed at MSK from 2008-2019. These trials included 92 patients, of which 14 (15%) were of ILC histology. Seven of 14 patients with ILC had an [18F]FDG PET/CT performed within 5 weeks of the research [18F]FES PET/CT and no intervening change in management. For these 7 patients, the [18F]FES and [18F]FDG PET/CT studies were analyzed to determine the total number of tracer avid lesions, organ systems of involvement, and SUVmax of each organ system for both tracers. Results: In the seven comparable pairs of scans, there were a total of 254 [18F]FES-avid lesions (SUVmax 2.6 to 17.9) and 111 [18F]FDG-avid lesions (SUVmax 3.3 to 9.9) suspicious for malignancy. For 5 of 7 (71%) of ILC patients, [18F]FES PET/CT detected more metastatic lesions than [18F]FDG PET/CT. In the same 5 of 7 patients, the SUVmax of [18F]FES-avid lesions was greater than the SUVmax of [18F]FDG-avid lesions. One patient had [18F]FES avid metastases with no corresponding [18F]FDG avid metastases. There were no patients with [18F]FDG avid distant metastases without [18F]FES avid distant metastases, although in one patient liver metastases were evident on [18F]FDG but not [18F]FES PET. Conclusion: [18F]FES PET/CT compared favorably with [18F]FDG PET/CT for detection of metastases in patients with metastatic ILC. Larger prospective trials of [18F]FES PET/CT in ILC should be considered to evaluate ER-targeted imaging for clinical value in patients with this histology of breast cancer.

We developed and tested the feasibility of computational fluid modeling (CFM) based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for quantitative estimation of interstitial fluid pressure (IFP) and velocity (IFV) in patients with head and neck (HN) cancer with locoregional lymph node metastases. Twenty-two patients with HN cancer, with 38 lymph nodes, underwent pretreatment standard MRI, including DCE-MRI, on a 3-Tesla scanner. CFM simulation was performed with the finite element method in COMSOL Multiphysics software. The model consisted of a partial differential equation (PDE) module to generate 3D parametric IFP and IFV maps, using the Darcy equation and Ktrans values (min−1, estimated from the extended Tofts model) to reflect fluid influx into tissue from the capillary microvasculature. The Spearman correlation (ρ) was calculated between total tumor volumes and CFM estimates of mean tumor IFP and IFV. CFM-estimated tumor IFP and IFV mean ± standard deviation for the neck nodal metastases were 1.73 ± 0.39 (kPa) and 1.82 ± 0.9 × (10−7 m/s), respectively. High IFP estimates corresponds to very low IFV throughout the tumor core, but IFV rises rapidly near the tumor boundary where the drop in IFP is precipitous. A significant correlation was found between pretreatment total tumor volume and CFM estimates of mean tumor IFP (ρ = 0.50, P = 0.004). Future studies can validate these initial findings in larger patients with HN cancer cohorts using CFM of the tumor in concert with DCE characterization, which holds promise in radiation oncology and drug-therapy clinical trials.

We aimed to compare the geometric distortion (GD) correction performance and apparent diffusion coefficient (ADC) measurements of single-shot diffusion-weighted echo-planar imaging (SS-DWEPI), multiplexed sensitivity encoding (MUSE)-DWEPI, and MUSE-DWEPI with reverse-polarity gradient (RPG) in phantoms and patients. We performed phantom studies at 3T magnetic resonance imaging (MRI) using the American College of Radiology phantom and Quantitative Imaging Biomarker Alliance DW-MRI ice-water phantom to assess GD and effect of distortion in the measurement of ADC, respectively. Institutional review board approved the prospective clinical component of this study. DW-MRI data were obtained from 11 patients with head and neck cancer using these three DW-MRI methods. Wilcoxon signed-rank (WSR) and Kruskal–Wallis (KW) tests were used to compare ADC values, and qualitative rating by radiologist between three DW-MRI methods. In the ACR phantom, GD of 0.17% was observed for the b = 0 s/mm2 image of the MUSE-DWEPI with RPG method compared with that of 1.53% and 2.1% of MUSE-DWEPI and SS-DWEPI, respectively, The corresponding methods root-mean-square errors were 0.58, 3.37, and 5.07 mm. WSR and KW tests showed no significant difference in the ADC measurement between these three DW-MRI methods for both healthy masseter muscles and neoplasms (P &gt, 05). We observed improvement in spatial accuracy for MUSE-DWEPI with RPG in the head and neck region with a higher correlation (R2 = 0.791) compared with that for SS-DWEPI (R2 = 0.707) and MUSE-DWEPI (R2 = 0.745). MUSE-DWEPI with RPG significantly reduces the distortion compared with MUSE-DWEPI or conventional SS-DWEPI techniques, and the ADC values were similar.

Purpose To demonstrate temporal lobe necrosis (TLN) rate and clinical/dose-volume factors associated with TLN in radiation-naïve patients with head and neck cancer treated with proton therapy where the field of radiation involved the skull base. Materials and Methods Medical records and dosimetric data for radiation-naïve patients with head and neck cancer receiving proton therapy to the skull base were retrospectively reviewed. Patients with Results Between 2013 and 2019, 234 patients were included. The median follow-up time was 22.5 months (range = 3.2–69.3). Overall TLN rates of any grade, ≥ grade 2, and ≥ grade 3 were 5.6% (N = 13), 2.1%, and 0.9%, respectively. The estimated 2-year TLN rate was 4.6%, and the 2-year rate of any brain necrosis was 6.8%. The median time to TLN was 20.9 months from proton completion. Absolute volume receiving 40, 50, 60, and 70 GyRBE (absolute volume [aV]); mean and maximum dose received by the temporal lobe; and dose to the 0.5, 1, and 2 cm3 volume receiving the maximum dose (D0.5cm3, D1cm3, and D2cm3, respectively) of the temporal lobe were associated with greater TLN risk while clinical parameters showed no correlation. Among volume parameters, aV50 gave maximum AUC (0.921), and D2cm3 gave the highest AUC (0.935) among dose parameters. The 11-cm3 cutoff value for aV50 and 62 GyRBE for D2cm3 showed maximum specificity and sensitivity. Conclusion The estimated 2-year TLN rate was 4.6% with a low rate of toxicities ≥grade 3; aV50 ≤11 cm3, D2cm3 ≤62 GyRBE and other cutoff values are suggested as constraints in proton therapy planning to minimize the risk of any grade TLN. Patients whose temporal lobe(s) unavoidably receive higher doses than these thresholds should be carefully followed with MRI after proton therapy.

Background Erdheim–Chester disease (ECD) is a rare histiocytic neoplasm characterized by recurrent alterations in the MAPK (mitogen-activating protein kinase) pathway. The existing literature about the neuro-oncological spectrum of ECD is limited. Methods We present retrospective clinical, radiographic, pathologic, molecular, and treatment data from 30 patients with ECD neurohistiocytic involvement treated at a tertiary center. Results Median age was 52 years (range, 7–77), and 20 (67%) patients were male. Presenting symptoms included ataxia in 19 patients (63%), dysarthria in 14 (47%), diabetes insipidus in 12 (40%), cognitive impairment in 10 (33%), and bulbar affect in 9 (30%). Neurosurgical biopsy specimens in 8 patients demonstrated varied morphologic findings often uncharacteristic of typical ECD lesions. Molecular analysis revealed mutations in BRAF (18 patients), MAP2K1 (5), RAS isoforms (2), and 2 fusions involving BRAF and ALK. Conventional therapies (corticosteroids, immunosuppressants, interferon-alpha [IFN-α], cytotoxic chemotherapy) led to partial radiographic response in 8/40 patients (20%) by MRI with no complete responses, partial metabolic response in 4/16 (25%), and complete metabolic response in 1/16 (6%) by 18F-fluorodeoxyglucose (FDG)-PET scan. In comparison, targeted (kinase inhibitor) therapies yielded partial radiographic response in 10/27 (37%) and complete radiographic response in 14/27 (52%) by MRI, and partial metabolic response in 6/25 (24%) and complete metabolic response in 17/25 (68%) by FDG-PET scan. Conclusions These data highlight underrecognized symptomatology, heterogeneous neuropathology, and robust responses to targeted therapies across the mutational spectrum in ECD patients with neurological involvement, particularly when conventional therapies have failed.

Histiocytic neoplasms are rare hematologic disorders characterized by pathologic infiltration of activated histiocytes in affected tissues. The treatment of histiocytic neoplasms, including Langerhans cell histiocytosis (LCH) and non-LCH, has advanced in recent years owing to targeted kinase inhibitors (BRAF and MEK) as patients with somatic mutations in the mitogen activated protein kinase (MAPK) pathway derive robust and durable responses with these therapies.1 However, there are patients with non-LCH who do not benefit from targeted therapies, particularly those with histiocytic infiltration of the nervous system, which is associated with mortality in 1 non-LCH disorder. BRAF and MEK inhibitors have limited penetration into the nervous system and worsening neurologic disease despite targeted therapy has been observed.2 These treatments can be limited or contraindicated by disease-related organ dysfunction or comorbidities. The subset of patients without MAPK alterations may not benefit from targeted therapies.

Imaging plays a vital role in diagnosing, planning, and monitoring treatment, and determining prognosis for head and neck and thyroid cancers. Ultrasound, CT, and MRI are first-line modalities for evaluating these tumors, and are excellent at characterizing tumor anatomy and relationship to surrounding structures. With the rise of advanced MRI in recent years, quantitative MRI has demonstrated promise in providing biomarkers for tumor histology, tumor aggressiveness, and prediction of clinical outcomes.

The present study aimed to investigate the correlation at pre-treatment (TX) between quantitative metrics derived from multimodality imaging (MMI), including 18F-FDG-PET/CT, 18F-FMISO-PET/CT, DW- and DCE-MRI, using a community detection algorithm (CDA) in head and neck squamous cell carcinoma (HNSCC) patients. Twenty-three HNSCC patients with 27 metastatic lymph nodes underwent a total of 69 MMI exams at pre-TX. Correlations among quantitative metrics derived from FDG-PET/CT (SUL), FMSIO-PET/CT (K1, k3, TBR, and DV), DW-MRI (ADC, IVIM [D, D*, and f]), and FXR DCE-MRI [Ktrans, ve, and τi]) were investigated using the CDA based on a “spin-glass model” coupled with the Spearman’s rank, ρ, analysis. Mean MRI T2 weighted tumor volumes and SULmean values were moderately positively correlated (ρ = 0.48, p = 0.01). ADC and D exhibited a moderate negative correlation with SULmean (ρ ≤ −0.42, p &lt, 0.03 for both). K1 and Ktrans were positively correlated (ρ = 0.48, p = 0.01). In contrast, Ktrans and k3max were negatively correlated (ρ = −0.41, p = 0.03). CDA revealed four communities for 16 metrics interconnected with 33 edges in the network. DV, Ktrans, and K1 had 8, 7, and 6 edges in the network, respectively. After validation in a larger population, the CDA approach may aid in identifying useful biomarkers for developing individual patient care in HNSCC.

Advances in imaging techniques, such as MR perfusion and spectroscopy, are increasingly indispensable in the management and treatment plans of brain neoplasms: from diagnosing, molecular/genetic typing and grading neoplasms, augmenting biopsy results and improving accuracy, to ultimately directing and monitoring treatment and response. New developments in treatment methods have resulted in new diagnostic challenges for conventional MR imaging, such as pseudoprogression, where MR perfusion has the widest current application. MR spectroscopy is showing increasing promise in noninvasively determining genetic subtypes and, potentially, susceptibility to molecular targeted therapies.

Current state-of-the-art models for estimating the pharmacokinetic parameters do not account for intervoxel movement of the contrast agent (CA). We introduce an optimal mass transport (OMT) formulation that naturally handles intervoxel CA movement and distinguishes between advective and diffusive flows. Ten patients with head and neck squamous cell carcinoma (HNSCC) were enrolled in the study between June 2014 and October 2015 and under-went DCE MRI imaging prior to beginning treatment. The CA tissue concentration information was taken as the input in the data-driven OMT model. The OMT approach was tested on HNSCC DCE data that provides quantitative information for forward flux (ΦF) and backward flux (ΦB). OMT-derived ΦF was compared with the volume transfer constant for CA, Ktrans, derived from the Extended Tofts Model (ETM). The OMT-derived flows showed a consistent jump in the CA diffusive behavior across the images in accordance with the known CA dynamics. The mean forward flux was 0.0082 ± 0.0091 (min-1) whereas the mean advective component was 0.0052±0.0086 (min-1) in the HNSCC patients. The diffusive percentages in forward and backward flux ranged from 8.67–18.76% and 12.76–30.36%, respectively. The OMT model accounts for intervoxel CA movement and results show that the forward flux (ΦF) is comparable with the ETM-derived Ktrans. This is a novel data-driven study based on optimal mass transport principles applied to patient DCE imaging to analyze CA flow in HNSCC.

ObjectiveTo perform a retrospective analysis examining the incidence and prognosis of glioma patients with leptomeningeal disease (LMD) at Memorial Sloan Kettering Cancer Center over a 15-year period and correlate these findings with clinicopathologic characteristics.MethodsWe conducted a retrospective review of glioma patients with LMD at Memorial Sloan Kettering Cancer Center diagnosed from 2001 to 2016. Patients were identified through a keyword search of their electronic medical record and by ICD-9 codes.ResultsOne hundred three patients were identified with disseminated LMD and 85 patients with subependymal spread of disease, 4.7% of all patients with glioma. These cohorts were analyzed separately for time to development of disseminated LMD/subependymal LMD, median overall survival, and survival from LMD diagnosis. Patients were pooled for subsequent analyses (n = 188) because of comparable clinical behavior. LMD was present at glioma diagnosis in 10% of patients. In the remaining 90% of patients diagnosed at recurrence, time to LMD diagnosis, survival after LMD diagnosis, and overall survival varied by original histology. Patients with oligodendroglioma had a median survival of 10.8 (range 1.8–67.7) months, astrocytoma 6.5 (0.1–28.5) months, and glioblastoma 3.8 (0.1–32.6) months after LMD diagnosis. In addition, we found that treatment of LMD was associated with superior performance status and increased survival.ConclusionPatients with LMD diagnosed at relapse may not have decreased overall survival as compared to historical controls with parenchymal relapse and may benefit from treatment.

The aim of this study was to establish the repeatability measures of quantitative Gaussian and non-Gaussian diffusion metrics using diffusion-weighted imaging (DWI) data from phantoms and patients with head-and-neck and papillary thyroid cancers. The Quantitative Imaging Biomarker Alliance (QIBA) DWI phantom and a novel isotropic diffusion kurtosis imaging phantom were scanned at 3 different sites, on 1.5T and 3T magnetic resonance imaging systems, using standardized multiple b-value DWI acquisition protocol. In the clinical component of this study, a total of 60 multiple b-value DWI data sets were analyzed for test–retest, obtained from 14 patients (9 head-and-neck squamous cell carcinoma and 5 papillary thyroid cancers). Repeatability of quantitative DWI measurements was assessed by within-subject coefficient of variation (wCV%) and Bland–Altman analysis. In isotropic diffusion kurtosis imaging phantom vial with 2% ceteryl alcohol and behentrimonium chloride solution, the mean apparent diffusion (Dapp × 10−3 mm2/s) and kurtosis (Kapp, unitless) coefficient values were 1.02 and 1.68 respectively, capturing in vivo tumor cellularity and tissue microstructure. For the same vial, Dapp and Kapp mean wCVs (%) were ≤1.41% and ≤0.43% for 1.5T and 3T across 3 sites. For pretreatment head-and-neck squamous cell carcinoma, apparent diffusion coefficient, D, D*, K, and f mean wCVs (%) were 2.38%, 3.55%, 3.88%, 8.0%, and 9.92%, respectively, wCVs exhibited a higher trend for papillary thyroid cancers. Knowledge of technical precision and bias of quantitative imaging metrics enables investigators to properly design and power clinical trials and better discern between measurement variability versus biological change.

Purpose: The goal of this study is to develop innovative methods for identifying radiomic features that are reproducible over varying image acquisition settings. Approach: We propose a regularized partial correlation network to identify reliable and reproducible radiomic features. This approach was tested on two radiomic feature sets generated using two different reconstruction methods on computed tomography (CT) scans from a cohort of 47 lung cancer patients. The largest common network component between the two networks was tested on phantom data consisting of five cancer samples. To further investigate whether radiomic features found can identify phenotypes, we propose a k-means clustering algorithm coupled with the optimal mass transport theory. This approach following the regularized partial correlation network analysis was tested on CT scans from 77 head and neck squamous cell carcinoma (HNSCC) patients in the Cancer Imaging Archive (TCIA) and validated using an independent dataset. Results: A set of common radiomic features was found in relatively large network components between the resultant two partial correlation networks resulting from a cohort of lung cancer patients. The reliability and reproducibility of those radiomic features were further validated on phantom data using the Wasserstein distance. Further analysis using the network-based Wasserstein k-means algorithm on the TCIA HNSCC data showed that the resulting clusters separate tumor subsites as well as HPV status, and this was validated on an independent dataset. Conclusion: We showed that a network-based analysis enables identifying reproducible radiomic features and use of the selected set of features can enhance clustering results.

Invasive lobular carcinoma (ILC) demonstrates lower conspicuity on (18)F-FDG PET than the more common invasive ductal carcinoma. Other molecular imaging methods may be needed for evaluation of this malignancy. As ILC is nearly always (95%) estrogen receptor (ER)–positive, ER-targeting PET tracers such as 16α-(18)F-fluoroestradiol ((18)F-FES) may have value. We reviewed prospective trials at Memorial Sloan Kettering Cancer Center using (18)F-FES PET/CT to evaluate metastatic ILC patients with synchronous (18)F-FDG and (18)F-FES PET/CT imaging, which allowed a head-to-head comparison of these 2 PET tracers. Methods: Six prospective clinical trials using (18)F-FES PET/CT in patients with metastatic breast cancer were performed at Memorial Sloan Kettering Cancer Center from 2008 to 2019. These trials included 92 patients, of whom 14 (15%) were of ILC histology. Seven of 14 patients with ILC had (18)F-FDG PET/CT performed within 5 wk of the research (18)F-FES PET/CT and no intervening change in management. For these 7 patients, the (18)F-FES and (18)F-FDG PET/CT studies were analyzed to determine the total number of tracer–avid lesions, organ systems of involvement, and SUV(max) of each organ system for both tracers. Results: In the 7 comparable pairs of scans, there were a total of 254 (18)F-FES–avid lesions (SUV(max), 2.6–17.9) and 111 (18)F-FDG–avid lesions (SUV(max), 3.3–9.9) suggestive of malignancy. For 5 of 7 (71%) ILC patients, (18)F-FES PET/CT detected more metastatic lesions than (18)F-FDG PET/CT. In the same 5 of 7 patients, the SUV(max) of (18)F-FES–avid lesions was greater than the SUV(max) of (18)F-FDG–avid lesions. One patient had (18)F-FES–avid metastases with no corresponding (18)F-FDG–avid metastases. There were no patients with (18)F-FDG–avid distant metastases without (18)F-FES–avid distant metastases, although in one patient liver metastases were evident on (18)F-FDG but not on (18)F-FES PET. Conclusion: (18)F-FES PET/CT compared favorably with (18)F-FDG PET/CT for detection of metastases in patients with metastatic ILC. Larger prospective trials of (18)F-FES PET/CT in ILC should be considered to evaluate ER-targeted imaging for clinical value in patients with this histology of breast cancer.

The aim of the present study was to identify whether the quantitative metrics from pre-treatment (TX) non-Gaussian intravoxel incoherent motion (NGIVIM) diffusion weighted (DW-) and fast exchange regime (FXR) dynamic contrast enhanced (DCE)-MRI can predict patients with locoregional failure (LRF) in nasopharyngeal carcinoma (NPC). Twenty-nine NPC patients underwent pre-TX DW- and DCE-MRI on a 3T MR scanner. DW imaging data from primary tumors were fitted to monoexponential (ADC) and NGIVIM (D, D*, f, and K) models. The metrics Ktrans, ve, and τi were estimated using the FXR model. Cumulative incidence (CI) analysis and Fine-Gray (FG) modeling were performed considering death as a competing risk. Mean ve values were significantly different between patients with and without LRF (p = 0.03). Mean f values showed a trend towards the difference between the groups (p = 0.08). Histograms exhibited inter primary tumor heterogeneity. The CI curves showed significant differences for the dichotomized cutoff value of ADC ≤ 0.68 × 10−3 (mm2/s), D ≤ 0.74 × 10−3 (mm2/s), and f ≤ 0.18 (p &lt, 0.05). τi ≤ 0.89 (s) cutoff value showed borderline significance (p = 0.098). FG’s modeling showed a significant difference for the K cutoff value of ≤0.86 (p = 0.034). Results suggest that the role of pre-TX NGIVIM DW- and FXR DCE-MRI-derived metrics for predicting LRF in NPC than alone.

Background Human epidermal growth factor receptor 2 (HER2)-targeted therapies are successful in patients with HER2-positive malignancies; however, spatial and temporal heterogeneity of HER2 expression may prevent identification of optimal patients for these therapies. Purpose To determine whether imaging with the HER2-targeted PET tracer zirconium 89 (

Introduction In ret proto-oncogene (RET)–rearranged lung cancers, data on the frequency of brain metastases and, in particular, the outcomes of multikinase inhibitor therapy in patients with intracranial disease are not well characterized. Methods A global, multi-institutional registry (cohort A, n = 114) and a bi-institutional data set (cohort B, n = 71) of RET-rearranged lung cancer patients were analyzed. Patients were eligible if they had stage IV lung cancers harboring a RET rearrangement by local testing. The incidence of brain metastases and outcomes with multikinase inhibitor therapy were determined. Results The frequency of brain metastases at the time of diagnosis of stage IV disease was 25% (95% confidence interval [CI]: 18%–32%) in all patients from both cohorts. The lifetime prevalence of brain metastasis in stage IV disease was 46% (95% CI: 34%–58%) in patients for whom longitudinal data was available. The cumulative incidence of brain metastases was significantly different (p = 0.0039) between RET-, ROS1-, and ALK receptor tyrosine kinase (ALK)–rearranged lung cancers, with RET intermediate between the other two groups. Although intracranial response data was not available in cohort A, the median progression-free survival of multikinase inhibitor therapy (cabozantinib, vandetanib, or sunitinib) in patients with brain metastases was 2.1 months (95% CI: 1.3–2.9 months, n = 10). In cohort B, an intracranial response was observed in 2 of 11 patients (18%) treated with cabozantinib, vandetanib (± everolimus), ponatinib, or alectinib; the median overall progression-free survival (intracranial and extracranial) was 3.9 months (95% CI: 2.0–4.9 months). Conclusions Brain metastases occur frequently in RET-rearranged lung cancers, and outcomes with multikinase inhibitor therapy in general are suboptimal. Novel RET-directed targeted therapy strategies are needed.

Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with NF-κB. The role of BTK in primary central nervous system (CNS) lymphoma (PCNSL) is unknown. We performed a phase I clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS lymphoma. Clinical responses to ibrutinib occurred in 10 of 13 (77%) patients with PCNSL, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of CARD11, a known ibrutinib resistance mechanism. Incomplete tumor responses were associated with mutations in the B-cell antigen receptor–associated protein CD79B. CD79B-mutant PCNSLs showed enrichment of mammalian target of rapamycin (mTOR)-related gene sets and increased staining with PI3K/mTOR activation markers. Inhibition of the PI3K isoforms p110α/p110δ or mTOR synergized with ibrutinib to induce cell death in CD79B-mutant PCNSL cells. Significance: Ibrutinib has substantial activity in patients with relapsed or refractory B-cell lymphoma of the CNS. Response rates in PCNSL were considerably higher than reported for diffuse large B-cell lymphoma outside the CNS, suggesting a divergent molecular pathogenesis. Combined inhibition of BTK and PI3K/mTOR may augment the ibrutinib response in CD79B-mutant human PCNSLs. Cancer Discov; 7(9); 1018–29. ©2017 AACR. See related commentary by Lakshmanan and Byrd, p. 940. This article is highlighted in the In This Issue feature, p. 920

BACKGROUND: Imaging criteria to evaluate the response of brain metastases to stereotactic radiosurgery (SRS) in the early posttreatment period remains a crucial unmet need. The aim of this study is to correlate early (within 12 wk) posttreatment perfusion MRI changes with long-term outcomes after treatment of lung cancer brain metastases with SRS. METHODS: Pre- and posttreatment perfusion MRI scans were obtained in patients treated with SRS for intact non–small cell lung cancer brain metastases. Time-dependent leakage (K(trans)), blood plasma volume (Vp), and extracellular extravascular volume (Ve) were calculated for each lesion. Patients were followed longitudinally with serial MRI until death, progression, or intervention (whole brain radiation or surgery). RESULTS: We included 53 lesions treated with SRS from 41 total patients. Median follow-up after treatment was 11 months. Actuarial local control at one year was 85%. Univariate analysis demonstrated a significant difference (P = 0.032) in posttreatment K(trans) SD between patients with progressive disease (mean = 0.0317) and without progressive disease (mean = 0.0219). A posttreatment K(trans) SD cutoff value of 0.017 was highly sensitive (89%) for predicting progressive disease and no progressive disease. Early posttreatment volume change was not associated with outcome (P = 0.941). CONCLUSION: Posttreatment K(trans) SD may be used as an early posttreatment imaging biomarker to help predict long-term response of lung cancer brain metastases to SRS. This can help identify patients who will ultimately fail SRS and allow for timelier adjustment in treatment approach. These data should be prospectively validated in larger patient cohorts and other histologies.

Brain metastases originating from different primary sites overlap in appearance and are difficult to differentiate with conventional MRI. Dynamic contrast‐enhanced (DCE)‐MRI can assess tumor microvasculature and has demonstrated utility in characterizing primary brain tumors. Our aim was to evaluate the performance of plasma volume (Vp) and volume transfer coefficient (K trans) derived from DCE‐MRI in distinguishing between melanoma and nonsmall cell lung cancer (NSCLC) brain metastases. Forty‐seven NSCLC and 23 melanoma brain metastases were retrospectively assessed with DCE‐MRI. Regions of interest were manually drawn around the metastases to calculate Vpmean and Kmeantrans. The Mann–Whitney U test and receiver operating characteristic analysis (ROC) were performed to compare perfusion parameters between the two groups. The Vpmean of melanoma brain metastases (4.35, standard deviation [SD] = 1.31) was significantly higher (P = 0.03) than Vpmean of NSCLC brain metastases (2.27, SD = 0.96). The Kmeantrans values were higher in melanoma brain metastases, but the difference between the two groups was not significant (P = 0.12). Based on ROC analysis, a cut‐off value of 3.02 for Vpmean (area under curve = 0.659 with SD = 0.074) distinguished between melanoma brain metastases and NSCLC brain metastases (P

Background and purpose: In this study we investigated the ability of textures from T1-weighted MRI scans post-contrast (T1wpost) to identify the critical muscle(s) for radiation-induced trismus. Materials and methods: The study included ten cases (Trismus: ≥Grade 1), and ten age-sex-tumor-location-and-stage-matched controls treated with intensity-modulated radiotherapy to 70 Gy@2.12 Gy in 2005–2009. Trismus status and T1wPost were conducted within one year post-radiotherapy. For the masseter, lateral and medial pterygoids, and temporalis (M/LP/MP/T), 24 textures were extracted (Grey Level Co-Occurrence (GLCM), Histogram, and Shape). Univariate logistic regression with Bootstrapping (1000 populations) was applied to compare the muscle mean dose (Dmean) and textures between cases and controls (ipsilateral muscles); candidate predictors were suggested by an average p ≤ 0.20 across all Bootstrap populations. Results: Dmean to M/LP/MP (p = 0.03/0.14/0.09), one MP/T (p = 0.12/0.17), and three M (p = 0.14–0.19) textures were candidate predictors. Three of these textures were GLCM- and two Histogram textures with the former being generally higher and the latter lower for cases compared to controls. The Dmean to M and MP, and Haralick Correlation (GLCM) of MP presented with the best discriminative ability (area under the receiver-operating characteristic curve: 0.85, 0.77, and 0.78), and the correlation between Dmean and this texture was weak (Spearman’s rank correlation coefficient: 0.26–0.27). Conclusions: Our exploratory study points towards an interplay between the dose to the masseter, and the medial pterygoid together with the local relationship between the mean MRI intensity relative to its variance of the medial pterygoid for radiation-induced trismus. This opens up for exploration of this interplay within the radiation-induced trismus etiology in the larger multi-institutional setting. Keywords: Head and neck cancer, Radiotherapy, Trismus, Quantitative image, Texture, Radiomics

AIM To noninvasively investigate tumor cellularity measured using diffusion-weighted magnetic resonance imaging (DW-MRI) and glucose metabolism measured by 18F-labeled fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) during radiation therapy (RT) for human papillomavirus negative (HPV-) head and neck squamous cell carcinoma (HNSCC). METHODS In this prospective study, 6 HPV- HNSCC patients underwent a total of 34 multimodality imaging examinations DW-MRI at 1.5 T Philips MRI scanner [(n = 24) pre-, during- (2-3 wk), and post-treatment (Tx), and 18F-FDG PET/CT pre- and post-Tx (n = 10)]. All patients received RT. Monoexponential modeling of the DW-MRI data yielded the imaging metric apparent diffusion coefficient (ADC) and the mean of standardized uptake value (SUV) was measured from 18F-FDG PET uptake. All patients had a clinical follow-up as the standard of care and survival status was documented at 1 year. RESULTS There was a strong negative correlation between the mean of pretreatment ADC (ρ = -0.67, P = 0.01) and the pretreatment 18F-FDG PET SUV. The percentage (%) change in delta (∆) ADC for primary tumors and neck nodal metastases between pre- and Wk2-3 Tx were as follows: 75.4% and 61.6%, respectively, for the patient with no evidence of disease, 27.5% and 32.7%, respectively, for those patients who were alive with disease, and 26.9% and 7.31%, respectively, for those who were dead with disease. CONCLUSION These results are preliminary in nature and are indicative, and not definitive, trends rendered by the imaging metrics due to the small sample size of HPV- HNSCC patients in a Meixoeiro Hospital of Vigo Experience.

We present an exceedingly rare case of a Ewing sarcoma metastasis manifesting as a sellar mass mimicking a pituitary adenoma. The differential diagnosis of the young adult with a sellar mass is presented and correlated with a review of available literature, demonstrating this case's unique potential for clinical teaching. More specifically, this case illustrates that in a patient with a clinical history of Ewing sarcoma, a metastasis may involve the sella and suprasellar cistern without apparent osseous involvement.

BACKGROUND AND PURPOSE: Glioblastoma and primary CNS lymphoma dictate different neurosurgical strategies; it is critical to distinguish them preoperatively. However, current imaging modalities do not effectively differentiate them. We aimed to examine the use of DWI and T1-weighted dynamic contrast-enhanced–MR imaging as potential discriminative tools. MATERIALS AND METHODS: We retrospectively reviewed 18 patients with primary CNS lymphoma and 36 matched patients with glioblastoma with pretreatment DWI and dynamic contrast-enhanced–MR imaging. VOIs were drawn around the tumor on contrast-enhanced T1WI and FLAIR images; these images were transferred onto coregistered ADC maps to obtain the ADC and onto dynamic contrast-enhanced perfusion maps to obtain the plasma volume and permeability transfer constant. Histogram analysis was performed to determine the mean and relative ADCmean and relative 90th percentile values for plasma volume and the permeability transfer constant. Nonparametric tests were used to assess differences, and receiver operating characteristic analysis was performed for optimal threshold calculations. RESULTS: The enhancing component of primary CNS lymphoma was found to have significantly lower ADCmean (1.1 × 10−3 versus 1.4 × 10−3; P CONCLUSIONS: ADC was superior to dynamic contrast-enhanced–MR imaging perfusion, alone or in combination, in differentiating primary CNS lymphoma from glioblastoma.

PurposeTo construct robust and validated radiomic predictive models, the development of a reliable method that can identify reproducible radiomic features robust to varying image acquisition methods and other scanner parameters should be preceded with rigorous validation. Due to the property of high correlation present between radiomic features, we hypothesize that reproducible radiomic features across different datasets that are obtained from different image acquisition settings preserve some level of connectivity between features in the form of a network.MethodsWe propose a regularized partial correlation network to identify robust and reproducible radiomic features. This approach was tested on two radiomic feature sets generated with two different reconstruction methods from a cohort of 47 lung cancer patients. The commonality of the resulting two networks was assessed. A largest common network component from the two networks was tested on phantom data consisting of 5 cancer samples. We further propose a novel K-means algorithm coupled with the optimal mass transport (OMT) theory to cluster samples. This approach following the regularized partial correlation analysis was tested on computed tomography (CT) scans from 77 head and neck cancer patients that were downloaded from The Cancer Imaging Archive (TCIA) and validated on CT scans from 83 head and neck cancer patients treated at our institution.ResultsCommon radiomic features were found in relatively large network components between the resulting two partial correlation networks from a cohort of 47 lung cancer patients. The similarity of network components in terms of the common number of radiomic features was statistically significant. For phantom data, the Wasserstein distance on a largest common network component from the lung cancer data was much smaller than the Wasserstein distance on the same network using random radiomic features, implying the reliability of those radiomic features present in the network. Further analysis using the proposed Wasserstein K-means algorithm on TCIA head and neck cancer data showed that the resulting clusters separate tumor subsites and this was validated on our institution data.ConclusionsWe showed that a network-based analysis enables identifying reproducible radiomic features. This was validated using phantom data and external data via the Wasserstein distance metric and the proposed Wasserstein K-means method.

We assessed a priori aggressive features using quantitative diffusion-weighted imaging metrics to preclude an active surveillance management approach in patients with papillary thyroid cancer (PTC) with tumor size 1–2 cm. This prospective study enrolled 24 patients with PTC who underwent pretreatment multi-b-value diffusion-weighted imaging on a GE 3 T magnetic resonance imaging scanner. The apparent diffusion coefficient (ADC) metric was calculated from monoexponential model, and the perfusion fraction (f), diffusion coefficient (D), pseudo-diffusion coefficient (D*), and diffusion kurtosis coefficient (K) metrics were estimated using the non-Gaussian intravoxel incoherent motion model. Neck ultrasonography examination data were used to calculate tumor size. The receiver operating characteristic curve assessed the discriminative specificity, sensitivity, and accuracy between PTCs with and without features of tumor aggressiveness. Multivariate logistic regression analysis was performed on metrics using a leave-1-out cross-validation method. Tumor aggressiveness was defined by surgical histopathology. Tumors with aggressive features had significantly lower ADC and D values than tumors without tumor-aggressive features (P &lt, 05). The absolute relative change was 46% in K metric value between the 2 tumor types. In total, 14 patients were in the critical size range (1–2 cm) measured by ultrasonography, and the ADC and D were significantly different and able to differentiate between the 2 tumor types (P &lt, 05). ADC and D can distinguish tumors with aggressive histological features to preclude an active surveillance management approach in patients with PTC with tumors measuring 1–2 cm.

BACKGROUND AND PURPOSE: A recent study using task-based fMRI demonstrated that the middle frontal gyrus is comparable with Broca9s area in its ability to determine language laterality using a measure of verbal fluency. This study investigated whether the middle frontal gyrus can be used as an indicator for language-hemispheric dominance in patients with brain tumors using task-free resting-state fMRI. We hypothesized that no significant difference in language lateralization would occur between the middle frontal gyrus and Broca area and that the middle frontal gyrus can serve as a simple and reliable means of measuring language laterality. MATERIALS AND METHODS: Using resting-state fMRI, we compared the middle frontal gyrus with the Broca area in 51 patients with glial neoplasms for voxel activation, the language laterality index, and the effect of tumor grade on the laterality index. The laterality index derived by resting-state fMRI and task-based fMRI was compared in a subset of 40 patients. RESULTS: Voxel activations in the left middle frontal gyrus and left Broca area were positively correlated ( r = 0.47, P r = 0.56, P CONCLUSIONS: The middle frontal gyrus is comparable with the Broca area in its ability to determine hemispheric dominance for language using resting-state fMRI. Our results suggest the addition of resting-state fMRI of the middle frontal gyrus to the list of noninvasive modalities that could be used in patients with gliomas to evaluate hemispheric dominance of language before tumor resection. In patients who cannot participate in traditional task-based fMRI, resting-state fMRI offers a task-free alternate to presurgically map the eloquent cortex.

BACKGROUND The purpose of this study was to investigate the utility and clinical impact of second-opinion interpretations of outside neuroimaging studies by oncologic neuroradiologists at a National Cancer Institute–designated cancer center. METHODS We performed a retrospective analysis of initial outside and second-opinion radiology reports from 300 computed tomography and magnetic resonance imaging studies and identified cases with discrepancies between the two reports. An adult neuro-oncologist, pediatric neuro-oncologist, and head and neck surgeon reviewed each pair of discrepant reports based on their area of expertise, patient age, and the type of study performed. The clinicians were blinded to the origin of each report and recorded whether the differences in the reports would have led to a change in patient management and/or disease staging. Histopathologic analysis, clinical assessment, and/or minimum 3-month imaging follow-up served as the reference standards to establish which of the 2 reports was correct. RESULTS Among the 283 cases that met our study criteria, there were 55 neuroimaging studies with disagreements (19%) between the initial outside report and second-opinion interpretation. Patient management and/or disease stage would have been altered in 42 of 283 cases (15%) based on report differences as determined by the 2 neuro-oncologists and the surgeon participating in the study. Sufficient follow-up was available in 35 of 42 cases (83%). The second-opinion interpretation was correct 100% of the time (35/35). CONCLUSION Second-opinion interpretations of neuroimaging studies by subspecialized oncologic neuroradiologists provide added value by reducing error and optimizing the care of cancer patients. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2708–2714. © 2016 American Cancer Society.

BACKGROUND AND PURPOSE Low-grade and anaplastic oligodendrogliomas are often difficult to differentiate on the basis of conventional MR imaging characteristics. Dynamic contrast-enhanced (DCE) MRI can assess tumor microvasculature and has demonstrated utility for predicting glioma grade and prognosis in primary brain tumors. The aim of our study was to evaluate the performance of plasma volume (Vp) and volume transfer coefficient (Ktrans) derived from DCE MRI in differentiating between grade II and grade III oligodendrogliomas. MATERIALS AND METHODS Twenty-four consecutive patients with pathologically confirmed oligodendroglioma (World Health Organization grade II, n = 14 and grade III, n = 10) were retrospectively assessed. Pretreatment DCE MRI was performed and regions of interest were manually drawn around the entire tumor volume to calculate Vp and Ktrans. The Mann-Whitney U test and receiver operating characteristic (ROC) analysis were performed to compare pharmacokinetic parameters between the 2 groups. RESULTS The Vpmean values for grade III oligodendrogliomas were significantly higher (P = .03) than those for grade II oligodendrogliomas. The Ktransmean values were higher in grade III lesions, but the difference between the 2 groups was not statistically significant (P > .05). Based on ROC analysis, the Vpmean (area under curve = .757, SD = .1) cut-off value that provided the best combination of high sensitivity and specificity to distinguish between grade II and III oligodendrogliomas was 2.35 (P < .03). CONCLUSION The results of our study suggest the DCE MRI parameter Vpmean can noninvasively differentiate between grade II and grade III oligodendrogliomas.

Purpose: Patients with cancers of oropharynx have a favorable prognosis and are an ideal candidate for adaptive therapy. A replan to improve coverage or escalate/de-escalate dose based on morphological information alone may not be adequate as the grossly involved lymph nodes (LNs) of a subset of these patients tend to become cystic and often do not regress. Functional adaptation may be a better approach when considering replanning for these patients. The purpose of this study was to evaluate the weekly trends in treatment related morphological and physiological changes for these LNs using diffusion-weighted MRI (DW-MRI) and evaluate its implications for adaptive replanning. Methods: Ten patients with histologically proven oropharynx HNSCC undergoing concurrent chemoradiation were analyzed in this study. MR imaging protocol included axial T1w, T2w, and DW-MRI using a 3 T Philips MR scanner. The patients were scanned weekly in radiation treatment planning position using a 16 element phased-array anterior coil and a 44 element posterior coil. A total of 65 DWI and T2w scans were analyzed. DWI was performed using an optimized single-shot echo planar imaging sequence (TR/TE = 5000/65 ms, slice thickness = 5 mm; slices = 28; b values = 0 and 800 s/mm2). Quantification of the DW-MRI images was performed by calculating the apparent diffusion coefficient (ADC). T2w and DWI scans were imported into the Eclipse treatment planning system and gross tumor volumes (GTVs) corresponding to grossly involved LNs were contoured on each axial slice by physician experts. An attempt was made to remove any cystic or necrotic components so that the ADC analysis was of viable tumor only. A pixel-by-pixel fit of signal intensities within the GTVs was performed assuming monoexponential behavior. From each GTV histogram mean, median, standard deviation, skewness, and kurtosis were calculated. Absolute and percent change in weekly ADC histogram parameters and percent change in T2w GTV were also calculated. Results: For all nodes, an immediate change in ADC was observed during first 2–3 weeks after which ADC values either continued to increase or plateaued. A few nodal volumes had a slightly decreased ADC value during later weeks. Percent increase in median ADC from weeks 1 to 6 with respect to baseline was 14%, 25%, 41%, 42%, 45%, and 58%. The corresponding change in median T2 volumes was 8%, 10%, 16%, 22%, 40%, and 42%, respectively. The ADC distribution of the viable tumors was initially highly kurtotic; however, the kurtosis decreased as treatment progressed. The ADC distribution also showed a higher degree of skewness in the first 2 weeks, progressively becoming less skewed as treatment progressed so as to slowly approach a more symmetric distribution. Conclusions: Physiological changes in LNs represented by changes in ADC evaluated using DW-MRI are evident sooner than the morphological changes calculated from T2w MRI. The decisions for adaptive replanning may need to be individualized and should be based primarily on tumor functional information. The authors’ data also suggest that for many patients, week 3 maybe the optimal time to intervene and replan. Larger studies are needed to confirm their findings.