Imaging Biomarker In Patients Research Articles

Epicardial adipose tissue radiodensity is associated with all-cause mortality in patients undergoing hemodialysis

The radiodensity and volume of epicardial adipose tissue (EAT) on computed tomography angiography (CTA) may provide information regarding cardiovascular risk and long-term outcomes. EAT volume is associated with mortality in patients undergoing incident hemodialysis. However, the relationship between EAT radiodensity/volume and all-cause mortality in patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis remains elusive. In this retrospective study, EAT radiodensity (in Hounsfield units) and volume (in cm3) on coronary CTA were quantified for patients with ESRD using automatic, quantitative measurement software between January 2012 and December 2018. All-cause mortality data (up to December 2019) were obtained from the Korean National Statistical Office. The prognostic values of EAT radiodensity and volume for predicting long-term mortality were assessed using multivariable Cox regression models, which were adjusted for potential confounders. A total of 221 patients (mean age: 64.88 ± 11.09 years; 114 women and 107 men) with ESRD were included. The median follow-up duration (interquartile range) after coronary CTA was 29.63 (range 16.67–44.7) months. During follow-up, 82 (37.1%) deaths occurred. In the multivariable analysis, EAT radiodensity (hazard ratio [HR] 1.055; 95% confidence interval [CI] 1.015–1.095; p = 0.006) was an independent predictor of all-cause mortality in patients with ESRD. However, EAT volume was not associated with mortality. Higher EAT radiodensity on CTA is associated with higher long-term all-cause mortality in patients undergoing prevalent hemodialysis, highlighting its potential as a prognostic imaging biomarker in patients undergoing hemodialysis.

Clinical Evaluation of a Fully-Automatic, CNN-based Analysis of Cardiac MRI Suggests Active Left Atrial Ejection Fraction as a Potential Imaging Biomarker in Patients with Atrial Fibrillation

Clinical Evaluation of a Fully-Automatic, CNN-based Analysis of Cardiac MRI Suggests Active Left Atrial Ejection Fraction as a Potential Imaging Biomarker in Patients with Atrial Fibrillation

Effect of oxaliplatin plus 5-fluorouracil or capecitabine on circulating and imaging biomarkers in patients with metastatic colorectal cancer: a prospective biomarker study

BackgroundPatients with metastatic colorectal cancer are treated with cytotoxic chemotherapy supplemented by molecularly targeted therapies. There is a critical need to define biomarkers that can optimise the use of these therapies to maximise efficacy and avoid unnecessary toxicity. However, it is important to first define the changes in potential biomarkers following cytotoxic chemotherapy alone. This study reports the impact of standard cytotoxic chemotherapy across a range of circulating and imaging biomarkers.MethodsA single-centre, prospective, biomarker-driven study. Eligible patients included those diagnosed with colorectal cancer with liver metastases that were planned to receive first line oxaliplatin plus 5-fluorouracil or capecitabine. Patients underwent paired blood sampling and magnetic resonance imaging (MRI), and biomarkers were associated with progression-free survival (PFS) and overall survival (OS).ResultsTwenty patients were recruited to the study. Data showed that chemotherapy significantly reduced the number of circulating tumour cells as well as the circulating concentrations of Ang1, Ang2, VEGF-A, VEGF-C and VEGF-D from pre-treatment to cycle 2 day 2. The changes in circulating concentrations were not associated with PFS or OS. On average, the MRI perfusion/permeability parameter, Ktrans, increased in response to cytotoxic chemotherapy from pre-treatment to cycle 2 day 2 and this increase was associated with worse OS (HR 1.099, 95%CI 1.01–1.20, p = 0.025).ConclusionsIn patients diagnosed with colorectal cancer with liver metastases, treatment with standard chemotherapy changes cell- and protein-based biomarkers, although these changes are not associated with survival outcomes. In contrast, the imaging biomarker, Ktrans, offers promise to direct molecularly targeted therapies such as anti-angiogenic agents.

Modeling hepatocellular carcinoma cells dynamics by serolo-gical and imaging biomarkers in patients with response to sorafenib and/or regorafenib

Introduction: In advanced HCC the overall benefits of multi-kinase inhibitors are limited, but some patients show partial response (PR) and a few achieve complete response (CR). Bio-mathematical modeling of in-vivo cancer cell dynamics by radiomics combining digital imaging and serological biomarkers would provide a better understanding of PR/CR.

Value of dynamic contrast-enhanced magnetic resonance imaging for determining the plasma Epstein-Barr virus status and staging of nasopharyngeal carcinoma

AimTo determine the associations between dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) parameters and plasma Epstein-Barr virus (EBV) DNA status and nasopharyngeal carcinoma (NPC) stages. MethodsWe prospectively studied the DCE-MRI results of 47 patients with newly diagnosed NPC and their pre-treatment plasma EBV DNA levels. We recruited all patients who had undergone MRI (1.5 T) simulation at the radiation therapy department of our institute between January 2018–2019. Regions of interest were drawn at primary tumors, and DCE-MRI parameters, including mean values of Ktrans, Kep, Ve, and Vp, were recorded. Spearman's rank correlation was used to identify significant associations between the DCE-MRI parameters and the plasma EBV DNA level and NPC stages. Mann-Whitney U tests and unpaired t-test were performed to compare the DCE-MRI parameters among different groups and to identify optimal cut-off values using receiver operating characteristic curves. ResultsWe found that the DCE-MRI parameters correlated with the plasma EBV DNA levels and NPC stages. Positive plasma EBV DNA was correlated with lower Kep (optimal cut-off value, 2.1 min−1; area under the curve [AUC], 0.714) and higher Ve (optimal cut-off value, 0.675; AUC, 0.706). Ve higher than 0.765 (AUC, 0.678) was correlated with plasma EBV DNA (≥2300 copies mL−1). Higher Ktrans (cut-off value, 1.495 min−1) was correlated with high-T stage (AUC, 0.767) and high-stage group (AUC, 0.711). ConclusionsThe DCE-MRI parameters are correlated with the plasma EBV DNA status and NPC stages. Therefore, DCE-MRI findings may be used as imaging biomarkers for patients with NPC.

Clinical and prognostic value of tumor volumetric parameters in melanoma patients undergoing 18F-FDG-PET/CT: a comparison with serologic markers of tumor burden and inflammation

BackgroundTo investigate the association of tumor volumetric parameters in melanoma patients undergoing 18F-FDG-PET/CT with serologic tumor markers and inflammatory markers and the role as imaging predictors for overall survival.MethodsA patient cohort with advanced melanoma undergoing 18F-FDG-PET/CT for planning metastasectomy between 04/2013 and 01/2015 was retrospectively included. The volumetric PET parameters whole-body MTV and whole-body TLG as well as the standard uptake value (SUV) peak were quantified using 50%-isocontour volumes of interests (VOIs) and then correlated with the serologic parameters lactate dehydrogenase (LDH), S-100 protein, c-reactive protein (CRP) and alkaline phosphatase (AP). PET parameters were dichotomized by their respective medians and correlated with overall survival (OS) after PET/CT. OS was compared between patients with or without metastases and increased or not-increased serologic parameters.ResultsOne hundred seven patients (52 female; 65 ± 13.1yr.) were included. LDH was strongly associated with MTV (rP = 0.73, p < 0.001) and TLG (rP = 0.62, p < 0.001), and moderately associated with SUVpeak (rP = 0.55, p < 0.001). S-100 protein showed a moderate association with MTV (rP = 0.54, p < 0.001) and TLG (rP = 0.48, p < 0.001) and a weak association with SUVpeak (rP = 0.42, p < 0.001). A strong association was observed between CRP and MTV (rP = 0.66, p < 0.001) and a moderate to weak association between CRP and TLG (rP = 0.53, p < 0.001) and CRP and SUVpeak (rP = 0.45, p < 0.001). For differentiation between patients with or without metastases, receiver operating characteristic (ROC) analysis revealed a cut-off value of 198 U/l for serum LDH (AUC 0.81, sensitivity 0.80, specificity 0.72).Multivariate analysis for OS revealed that both MTV and TLG were strong independent prognostic factors. TLG, MTV and SUVpeak above patient median were accompanied with significantly reduced estimated OS compared to the PET parameters below patient median (e.g. TLG: 37.1 ± 3.2 months vs. 55.9 ± 2.5 months, p < 0.001). Correspondingly, both elevated serum LDH and S-100 protein were accompanied with significantly reduced OS (36.5 ± 4.9 months and 37.9 ± 4.4 months) compared to normal serum LDH (49.2 ± 2.4 months, p = 0.01) and normal S-100 protein (49.0 ± 2.5 months, p = 0.01).ConclusionsTumor volumetric parameters in 18F-FDG-PET/CT serve as prognostic imaging biomarkers in patients with advanced melanoma which are associated with established serologic tumor markers and inflammatory markers.

Volumetric 68Ga-DOTA-TATE PET/CT for assessment of whole-body tumor burden as a quantitative imaging biomarker in patients with metastatic gastroenteropancreatic neuroendocrine tumors.

A quantitative imaging biomarker is desirable to provide a comprehensive measure of whole-body tumor burden in patients with metastatic neuroendocrine tumors, and to standardize the evaluation of treatment-related changes. Therefore, we evaluated volumetric parameters for quantification of whole-body tumor burden from somatostatin receptor (SSR)-targeted PET/CT. Thirty-two patients with metastastic grade1/grade 2 gastroenteropancreatic neuroendocrine tumors who underwent a 68Ga-DOTA-TATE PET/CT for staging of disease before initiation of peptide receptor radionuclide therapy were included in this retrospective cohort analysis. Volumetric parameters of tumor lesions, SSR-derived tumor volume (SSR-TV) and total lesion SSR (TL-SSR), were calculated for each patient using a computerized volumetric technique with a 40% SUV<inf>max</inf> cut-off, and compared with serum chromogranin A (CgA) levels. Progression-free survival (PFS) was determined in relation to volumetric parameters. In a subgroup of 18 patients, the feasibility of volumetric parameters for treatment monitoring was evaluated. Mean SSR-TV was 178±214 cm3 (range, 9-797 cm3), whereas mean TL-SSR was 4096±5191 cm3 (range, 61-19,203 cm3). Baseline CgA levels were associated with whole-body tumor burden (SSR-TV, r=0.57, P=0.0008; and TL-SSR, r=0.43, P=0.01, respectively). PFS was shorter in patients with high SSR-TV and high TL-SSR (HR 5.16, 95% CI, 1.61-29.67), P=0.009), and SSR-TV (P=0.0067) and TL-SSR (P=0.0215) emerged as the sole predictors of progression in regression analysis. Changes in CgA did not correctly identify treatment response (P=0.25). SSR-derived volumetric parameters provide a quantitative imaging biomarker for whole-body tumor burden, and may hold potential as a clear-cut measure for assessment of treatment response.

Muscle ultrasound is a responsive biomarker in facioscapulohumeral dystrophy.

With drug trials starting soon, responsive, relevant, and patient-friendly biomarkers are highly needed in facioscapulohumeral dystrophy (FSHD). Our objective was to assess muscle ultrasound (MUS) as an imaging biomarker in patients with FSHD. One-year observational, longitudinal study of both quantitative and qualitative MUS changes in FSHD. Twenty-two patients with symptomatic FSHD1 underwent a clinical examination and MUS at baseline and after 1-year follow-up. The qualitative MUS sum score increased from 18.59 to 20.32 (p = 0.005) and the quantitative MUS sum z scores increased from 19.96 to 24.72 (p = 0.003). The clinical scores did not change over 1 year. Muscle echogenicity correlated with the FSHD clinical score at baseline (r = 0.61, p = 0.002). MUS shows a significant increase in echogenicity in FSHD over 1 year. Both quantitative and qualitative MUS correlate cross-sectionally with clinical severity in FSHD and identify structural muscle changes in a clinically stable group of patients. MUS thus seems a potentially responsive biomarker that could be standardized between centers. We recommend its use in therapeutic trials. This study provides Class I evidence that in patents with FSHD1, MUS findings correlate with baseline FSHD clinical scores.

Brain Imaging Biomarkers in Patients With Brain Metastasis

Brain Imaging Biomarkers in Patients With Brain Metastasis

Dynamic Contrast-Enhanced MR Imaging of Nonenhancing T2 High-Signal-Intensity Lesions in Baseline and Posttreatment Glioblastoma: Temporal Change and Prognostic Value.

The prognostic value of dynamic contrast-enhanced MR imaging on nonenhancing T2 high-signal-intensity lesions in patients with glioblastoma has not been thoroughly elucidated to date. We evaluated the temporal change and prognostic value for progression-free survival of dynamic contrast-enhanced MR imaging-derived pharmacokinetic parameters on nonenhancing T2 high-signal-intensity lesions in patients with glioblastoma before and after standard treatment, including gross total surgical resection. This retrospective study included 33 patients who were newly diagnosed with glioblastoma and treated with gross total surgical resection followed by concurrent chemoradiation therapy and adjuvant chemotherapy with temozolomide in a single institution. All patients underwent dynamic contrast-enhanced MR imaging before surgery as a baseline and after completion of maximal surgical resection and concurrent chemoradiation therapy. On the whole nonenhancing T2 high-signal-intensity lesion, dynamic contrast-enhanced MR imaging-derived pharmacokinetic parameters (volume transfer constant [K trans], volume of extravascular extracellular space [v e], and blood plasma volume [vp ]) were calculated. The Cox proportional hazards regression model analysis was performed to determine the histogram features or percentage changes of pharmacokinetic parameters related to progression-free survival. Baseline median K trans, baseline first quartile K trans, and posttreatment median K trans were significant independent variables, as determined by univariate analysis (P < .05). By multivariate Cox regression analysis including methylation status of O6-methylguanine-DNA methyltransferase, baseline median K trans was determined to be the significant independent variable and was negatively related to progression-free survival (hazard ratio = 1.48, P = .003). Baseline median K trans from nonenhancing T2 high-signal-intensity lesions could be a potential prognostic imaging biomarker in patients undergoing gross total surgical resection followed by standard therapy for glioblastoma.

Assessment of Orbital Computed Tomography (CT) Imaging Biomarkers in Patients with Thyroid Eye Disease.

To understand potential orbital biomarkers generated from computed tomography (CT) imaging in patients with thyroid eye disease. This is a retrospective cohort study. From a database of an ongoing thyroid eye disease research study at our institution, we identified 85 subjects who had both clinical examination and laboratory records supporting the diagnosis of thyroid eye disease and concurrent imaging prior to any medical or surgical intervention. Patients were excluded if imaging quality or type was not amenable to segmentation. The images of 170 orbits were analyzed with the developed automated segmentation tool. The main outcome measure was to cross 25 CT structural metrics for each eye with nine clinical markers using a Kendall rank correlation test to identify significant relationships. The Kendall rank correlation test between automatically calculated CT metrics and clinical data demonstrated numerous correlations. Extraocular rectus muscle metrics, such as the average diameter of the superior, medial, and lateral rectus muscles, showed a strong correlation (p < 0.05) with loss of visual acuity and presence of ocular motility defects. Hertel measurements demonstrated a strong correlation (p < 0.05) with volumetric measurements of the optic nerve and other orbital metrics such as the crowding index and proptosis. Optic neuropathy was strongly correlated (p < 0.05) with an increase in the maximum diameter of the superior muscle. This novel method of automated imaging metrics may provide objective, rapid clinical information. This data may be useful for appreciation of severity of thyroid eye disease and recognition of risk factors of visual impairment from dysthyroid optic neuropathy from CT imaging.

Clinical Imaging of Choroid Plexus in Health and in Brain Disorders: A Mini-Review.

The choroid plexuses (ChPs) perform indispensable functions for the development, maintenance and functioning of the brain. Although they have gained considerable interest in the last years, their involvement in brain disorders is still largely unknown, notably because their deep location inside the brain hampers non-invasive investigations. Imaging tools have become instrumental to the diagnosis and pathophysiological study of neurological and neuropsychiatric diseases. This review summarizes the knowledge that has been gathered from the clinical imaging of ChPs in health and brain disorders not related to ChP pathologies. Results are discussed in the light of pre-clinical imaging studies. As seen in this review, to date, most clinical imaging studies of ChPs have used disease-free human subjects to demonstrate the value of different imaging biomarkers (ChP size, perfusion/permeability, glucose metabolism, inflammation), sometimes combined with the study of normal aging. Although very few studies have actually tested the value of ChP imaging biomarkers in patients with brain disorders, these pioneer studies identified ChP changes that are promising data for a better understanding and follow-up of diseases such as schizophrenia, epilepsy and Alzheimer’s disease. Imaging of immune cell trafficking at the ChPs has remained limited to pre-clinical studies so far but has the potential to be translated in patients for example using MRI coupled with the injection of iron oxide nanoparticles. Future investigations should aim at confirming and extending these findings and at developing translational molecular imaging tools for bridging the gap between basic molecular and cellular neuroscience and clinical research.

Hepatic blood flow by perfusion computed tomography as an imaging biomarker for patients with gastric cancer.

Perfusion computed tomography (PCT) is a less invasive imaging modality that provides information about tissue hemodynamics at the capillary level. The present study aimed to investigate the correlation between hepatic perfusion and gastric cancer progression. A total of 136 patients with gastric adenocarcinoma were evaluated in the present study. Prior to initial treatment, liver PCT was performed across the hepatic hilar plane and the hepatic blood flow (HBF) was measured using the dual-input deconvolution method. HBF was compared with clinicopathological factors, patient prognosis and circulating serum proangiogenic cytokines. The median HBF was 217 ml/min/100 g tissue. Patients with high HBF had larger tumors (43 mm vs. 71, P<0.001) and more advanced tumor-node stages (P<0.001 for both). When both patient groups of operable and inoperable were compared by their respective median HBF values, each high-HBF group had a significantly worse prognosis (P=0.002 and P=0.024), notably in the inoperable group, with <1-year survival. In 17 postoperative recurrent patients, the high-HBF at recurrence group also had a significantly worse postrecurrent prognosis (P=0.019). HBF was an independent prognostic factor (hazard ratio, 2.019; P=0.048) and was strongly associated with serum vascular endothelial growth factor level (R=0.607, P<0.001). HBF was significantly correlated with gastric cancer progression, and is an easily measured imaging biomarker reflecting patient survival.

Dynamic contrast-enhanced magnetic resonance imaging in locally advanced rectal cancer: role ofperfusion parameters in the assessment of response to treatment.

To correlate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters to tumor grading and to assess their reliability in predicting pathological complete response (pCR) before neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC). Forty patients (24 male; mean age, 67.3 ± 8.1years) with histologically proven LARC who had undergone 3-Tesla DCE-MRI before (MRI_1) and after CRT (MRI_2) between August 2015 and February 2016 were included in this retrospective study. DCE-MRI parameters at MRI_1 and MRI_2 were extracted by two board certified radiologists in consensus reading with Olea Sphere 2.3 software using the extended Tofts model. Based on DCE-MRI results, patients were divided in complete responders (CR) and non-complete responders (nCR) and the perfusion parameters were correlated to tumor grading and pCR. Wash-out and Kep at MRI_1 showed significant correlation with LARC grading (P = 0.004 and 0.01, respectively). Ve showed a significant increase between MRI_1 (0.47 ± 0.27) and MRI_2 (0.63 ± 0.23; P = 0.007). Ktrans measured at MRI_1 was significantly higher in CR (0.66 ± 0.48) compared to nCR (0.53 ± 0.34, P = 0.02). Wash-out and Kep measured before CRT correlate with LARC grading. Ve changes during CRT, while Ktrans measured before CRT may predict the response to therapy. Therefore, DCE-MRI parameters can predict tumor aggressiveness and CRT efficacy, playing a role as imaging biomarkers in patients with LARC.

Modified fractal analysis of methionine positron emission tomography images for predicting prognosis in newly diagnosed patients with glioma.

To assess intratumoural metabolic heterogeneity using modified fractal analysis and to determine its prognostic significance in patients with glioma. A total of 57 patients with newly diagnosed glioma who underwent methionine PET-computed tomography between August 2012 and January 2017 were enrolled. The requirement for informed consent was waived for this retrospective study. Tumour-to-normal tissue ratio, metabolic tumour volume, total lesion methionine uptake and modified fractal dimension (m-FD) were calculated for each tumour using methionine PET-computed tomography. Associations between these indices and tumour grade and overall survival were analysed. Overall, eight patients had grade II, 20 had grade III and 29 had grade IV tumours. The tumour-to-normal tissue ratios of grade III and grade IV tumours were significantly greater than that of grade II tumours. The metabolic tumour volume and total lesion methionine uptake of grade III tumours were significantly greater than those of grade II and grade IV tumours. The m-FD of grade IV tumours was significantly greater than those of grade II and grade III tumours. A total of 47 patients were followed up, and their prognoses were evaluated. Only the m-FD was significantly associated with a poor prognosis (P<0.05). Multivariate analyses identified age (>58 years) (hazard ratio: 5.73; 95.0% confidence interval: 1.4-29.9; P=0.015) and the m-FD (>0.87) (hazard ratio: 4.80; 95.0% confidence interval: 1.12-32.9; P=0.033) as independent prognostic factors for overall survival. Intratumoural metabolic heterogeneity is a useful imaging biomarker in patients with glioma.

Predicting Per-Lesion Local Recurrence in Locally Advanced Lung Cancer using Metabolic Tumor Volume on Pre- and Mid-Radiation FDG-PET

PET metrics, including metabolic tumor volume (MTV), have been proposed as prognostic imaging biomarkers in patients treated with definitive radiation therapy (RT) for locally advanced non-small cell lung cancer (NSCLC). We evaluated whether the per-lesion change in MTV (ΔMTV) between pre- and mid-treatment PET can be used to predict individual sites of disease progression in this setting. We retrospectively reviewed the records of patients with stage III NSCLC treated with definitive RT (dose≥60 Gy) from 2006 to 2017. We included patients with pre- and mid-RT PET/CT and follow up >3 months. PET Edge, a gradient-based method included in a commercially available deformable registration algorithm, was used to delineate treated lesions (lung tumors and regional lymph nodes) and measure MTVs. The distributions of pre-RT (MTVpre) and mid-RT (MTVmid) MTVs were right-skewed and thus log transformed for analysis. ΔMTV was defined as (MTVmid-MTVpre)/MTVpre. Local recurrence (LR) was defined per lesion (lung tumor or lymph node) as recurrence within the planning target volume based on review of follow-up imaging. Cumulative incidence rates and uni- and multivariate (MVA) Cox regression were used to evaluate the association between ΔMTV and LR for each lesion. Models were adjusted for the competing risk of death. Receiver operating characteristic (ROC) curves were developed to assess the utility of MTV parameters as predictors of LR (R, version 3.3). We identified 80 patients with 272 treated lesions (84 lung tumors and 188 lymph nodes; median 3 lesions per patient). Patients had median age 68 years (IQR 64-76 years). 65% (n=52) of patients were male, 48.8% (n=39) had adenocarcinoma, and 36.3% (n=29) had squamous cell carcinoma. 73 (91.3%) patients received concurrent chemotherapy. Median follow-up was 14 months. Overall survival was 75.0% at 1 year and 50.6% at 2 years. Cumulative incidence of LR was 20.3% at 1 year and 21.3% at 2 years per lesion. When adjusting for lesion location (lung primary versus lymph node) and age in MVA, MTVpre (HR=1.47, 95% CI=1.09-1.99, p=0.02) and ΔMTV (HR=1.06, 95% CI=1.04-1.10, p<0.001) were significantly associated with LR. We did not observe a higher rate of LR for nodal vs primary lesions. We developed a point-based model (0-2) where target lesions accumulate 1 point each for MTVpre>25cc and decrease in ΔMTV<65%. At 1 year, lesions with 0, 1, and 2 points had predicted LR rates of 14%, 21%, and 36%, respectively (p=0.02). We found that high MTVpre and low ΔMTV were independently associated with per-lesion LR in locally advanced lung cancer, suggesting that both pre- and mid-RT PET provide complementary predictive information. If validated in larger cohorts, this may be the basis for designing adaptive dose painting strategies to maximize therapeutic index.

Prediction of Response to Neoadjuvant Chemotherapy and Radiation Therapy with Baseline and Restaging 18F-FDG PET Imaging Biomarkers in Patients with Esophageal Cancer.

Purpose To assess the value of baseline and restaging fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) radiomics in predicting pathologic complete response to neoadjuvant chemotherapy and radiation therapy (NCRT) in patients with locally advanced esophageal cancer. Materials and Methods In this retrospective study, 73 patients with histologic analysis-confirmed T1/N1-3/M0 or T2-4a/N0-3/M0 esophageal cancer were treated with NCRT followed by surgery (Chemoradiotherapy for Esophageal Cancer followed by Surgery Study regimen) between October 2014 and August 2017. Clinical variables and radiomic features from baseline and restaging 18F-FDG PET were selected by univariable logistic regression and least absolute shrinkage and selection operator. The selected variables were used to fit a multivariable logistic regression model, which was internally validated by using bootstrap resampling with 20 000 replicates. The performance of this model was compared with reference prediction models composed of maximum standardized uptake value metrics, clinical variables, and maximum standardized uptake value at baseline NCRT radiomic features. Outcome was defined as complete versus incomplete pathologic response (tumor regression grade 1 vs 2-5 according to the Mandard classification). Results Pathologic response was complete in 16 patients (21.9%) and incomplete in 57 patients (78.1%). A prediction model combining clinical T-stage and restaging NCRT (post-NCRT) joint maximum (quantifying image orderliness) yielded an optimism-corrected area under the receiver operating characteristics curve of 0.81. Post-NCRT joint maximum was replaceable with five other redundant post-NCRT radiomic features that provided equal model performance. All reference prediction models exhibited substantially lower discriminatory accuracy. Conclusion The combination of clinical T-staging and quantitative assessment of post-NCRT 18F-FDG PET orderliness (joint maximum) provided high discriminatory accuracy in predicting pathologic complete response in patients with esophageal cancer. © RSNA, 2018 Online supplemental material is available for this article.

Evaluation of the lamina cribrosa in patients with multiple sclerosis using enhanced depth imaging optical coherence tomography

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. Optic neuritis (ON) is common clinical manifestation of MS. Spectral domain optical coherence tomography (SD-OCT) has been used as a useful tool to quantify the neuronal damage in the eyes of MS patients. The study aimed to evaluate the lamina cribrosa thickness (LCT) and lamina cribrosa depth (LCD) in patients with MS and their relationship with Expanded Disability Status Scale (EDSS) score. Fifty-two eyes of 26 relapsing-remitting MS patients and 39 eyes of 39 healthy age- and sex- matched participants were evaluated in this prospective, cross-sectional, observational study. There were two MS subgroups: 38 MS eyes without an ON history (MS−ON), and 14 MS eyes with an ON history (MS+ON). The LCT and LCD were measured with SD-OCT. Of the 26 participants with MS, 14 (53.8%) were female and the mean (SD) age was 35.1 (6.2) years; of the 39 healthy controls, 26 (66.7%) were female and the mean (SD) age was 36.7 (8.2) years (P=0.19 for sex and P=0.27 for age). The mean LCT was not significantly different between MS patients and healthy controls (272.66 ± 33.52 μm and 272.58 ± 35.97 μm, respectively, P=0.992). The mean LCD was 325.15 ± 67.07 μm for the MS+ON group, 409.71 ± 93.18 μm for the MS−ON group, and 427.64 ± 91.65 μm for the healthy control group. The LCD was significantly decreased in MS+ON group compared to MS−ON group (P=0.011) and healthy controls (P=0.002). EDSS score was negatively correlated with LCD in MS patients (r= -0.313, P=0.025). This study revealed decreased LCD in MS eyes particularly with optic neuritis, and its relationship with increased disease severity. Additional longitudinal studies are needed to confirm the use of LCD as an imaging biomarker in patients with MS.

T2 signal intensity as an imaging biomarker for patients with superficial Fibromatoses of the hands (Dupuytren's disease) and feet (Ledderhose disease) undergoing definitive electron beam irradiation.

Electron beam therapy is a definitive radiation treatment option for superficial fibromatoses of the hands and feet. Because objective criteria for treatment response remain poorly defined, we sought to describe changes in electron beam treated lesions on MRI. The study included 1 male and 9 female patients with a total of 37 superficial fibromatoses; average age was 60.7years. Standard 6MeV electron beam treatment included 3Gy per fraction for 10 or 12 treatments using split-course with 3-month halfway break. Pre- and post-treatment MRIs were evaluated to determine lesion size (cm3), T2 signal intensity and contrast enhancement (5-point ordinal scales) by a fellowship trained musculoskeletal radiologist. MRI findings were correlated with clinical response using a composite 1-5 ordinal scale, Karnofsky Performance Scale and patient-reported 10-point visual analog scale for pain. Mean volume decreased from 1.5 to 1.2cm3 (p=0.01, paired t-test). Mean T2 hyperintensity score decreased from 3.0 to 2.1 (p<0.0001, Wilcoxon signed-rank). Mean enhancement score available for 22 lesions decreased from 3.8 to 3.0 (p<0.0001, Wilcoxon signed-rank). Performance scores improved from 78.9 ± 13.7 to 84.6 ± 6.9 (p=0.007, paired t-test). Pain scores decreased from 3.0 ± 3.3 to 1.1 ± 2.0 (p=0.0001, paired t-test). Post-treatment T2 signal correlated weakly with performance and pain (Spearman's ρ=-0.37 and 0.16, respectively). MRI is valuable for evaluating patients undergoing electron beam therapy for superficial fibromatoses: higher pretreatment T2 intensity may predict benefit from radiotherapy. T2 hypointensity may be a better marker than size for therapeutic effect.

Subcutaneous Adipose Tissue Characteristics and Risk of Biochemical Recurrence in Men with High Risk Prostate Cancer

Obesity has become a worldwide epidemic. The interaction of obesity and excess adipose tissue on cancer biology continues to be an area of interest. The purpose of this study was to assess subcutaneous adipose tissue characteristics by computed tomography (CT) as potential imaging biomarkers in patients with high risk prostate cancer receiving radiation treatment (RT). This retrospective study included 185 men with high risk prostate cancer (PSA>20 ng/mL, Gleason score ≥ 8, or clinical extraprostatic extension) treated between 2001 and 2012. All patients received definitive, dose-escalated external beam RT along with a course of neoadjuvant, concurrent, and adjuvant androgen deprivation therapy (ADT). Each patient also had a treatment planning CT that included the L4-L5 vertebral interface and prostate specific antigen (PSA) measurements for at least 1 year following RT. The subcutaneous adipose tissue was contoured on a single axial CT slice at the level of L4-L5. The average CT attenuation, in Hounsfield units (HU), of the structure was calculated and defined as SATHU. SATAREA was defined as the cross-sectional area of the structure (in cm2) that was then normalized by the square of patient height. Biochemical failure (BF) was defined as a PSA rise of 2 ng/mL from the nadir. Freedom from BF (FFBF) was calculated from start time of ADT using the Kaplan-Meier method. Estimates of FFBF were stratified by SATHU and SATAREA quartiles. Median follow-up was 5.3 years. The mean SATHU (± standard deviation) was -99.2 HU (±6.3 HU) and the mean SATAREA was 94.7 cm2/m2 (±42.3 cm2/m2). No significant differences of SATHU and SATAREA were observed among different races or age groups. The 5 and 8-year rates of FFBF across all patients were 82.1% and 74%, respectively. Patients in the lowest quartile of SATHU experienced significantly higher FFBF compared to the other quartiles (Q4 vs. Q1, p=0.029; Q4 vs. Q2, p=0.045; Q4 vs. Q3, p=0.045). No other differences in FFBF were observed between quartiles of SATAREA or other quartiles of SATHU. Using CT imaging as a novel prognostic biomarker, low attenuation of abdominal adipose tissue was associated with a lower rate of biochemical failure in patients with high risk prostate cancer. Further research is needed to elucidate the biological underpinnings of this clinical finding and the role adipose tissue plays in modulating oncologic behavior and outcomes.