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1.  Comparing primary tumors and metastatic nodes in head and neck cancer using intravoxel incoherent motion imaging: a preliminary experience 
Journal of computer assisted tomography  2013;37(3):10.1097/RCT.0b013e318282d935.
To use intravoxel incoherent motion (IVIM) imaging for investigating differences between primary head and neck tumors and nodal metastases and evaluating IVIM efficacy in predicting outcome.
Sixteen patients with HN cancer underwent IVIM DWI on a 1.5T MRI scanner. The significance of parametric difference between primary tumors and metastatic nodes were tested. Probabilities of progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.
In comparison to metastatic nodes, the primary tumors had significantly higher vascular volume fraction (f) (p<0.0009), and lower diffusion coefficient (D) (p<0.0002). Patients with lower standard deviation for D had prolonged PFS and OS (p<0.05).
Pretreatment IVIM measures were feasible in investigating the physiological differences between the two tumor tissues. After appropriate validation, these findings might be useful in optimizing treatment planning and improving patient care.
PMCID: PMC3655331  PMID: 23674004
Intravoxel incoherent motion imaging (IVIM); head and neck (HN) cancer; primary tumor; metastatic neck node
2.  Extension of the Intravoxel Incoherent Motion Model to Non-Gaussian Diffusion in Head and Neck Cancer 
To extend the intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) model to restricted diffusion and to simultaneously quantify the perfusion and restricted diffusion parameters in neck nodal metastases.
Materials and Methods
The non-Gaussian (NG)-IVIM model was developed and tested on diffusion-weighted MRI data collected on a 1.5-Tesla MRI scanner from 8 patients with head and neck cancer. Voxel-wise parameter quantification was performed by using a noise-rectified least-square fitting method. The NG-IVIM, IVIM, Kurtosis, and ADC (apparent diffusion coefficient) models were used for comparison. For each voxel, within the metastatic node, the optimal model was determined using the Bayesian Information Criterion. The voxel percentage preferred by each model was calculated and the optimal model map was generated. Monte Carlo simulations were performed to evaluate the accuracy and precision dependency of the new model.
For the 8 neck nodes, the range of voxel percentage preferred by the NG-IVIM model was 2.3% - 79.3%. The optimal modal maps showed heterogeneities within the tumors. The Monte Carlo simulations demonstrated that the accuracy and precision of the NG-IVIM model improved by increasing signal-to-noise ratio and b value.
The NG-IVIM model characterizes perfusion and restricted diffusion simultaneously in neck nodal metastases.
PMCID: PMC3482143  PMID: 22826198
Intravoxel incoherent motion; noise rectification; restricted diffusion; perfusion
3.  Correlation of a priori DCE-MRI and 1H-MRS data with molecular markers in neck nodal metastases: Initial analysis 
Oral oncology  2012;48(8):717-722.
The aim of the present study is to correlate non-invasive, pretreatment biological imaging (dynamic contrast enhanced-MRI [DCE-MRI] and proton magnetic resonance spectroscopy [1H-MRS]) findings with specific molecular marker data in neck nodal metastases of head and neck squamous cell carcinoma (HNSCC) patients.
Materials and Methods
Pretreatment DCE-MRI and 1H-MRS were performed on neck nodal metastases of 12 patients who underwent surgery. Surgical specimens were analyzed with immunohistochemistry (IHC) assays for: Ki-67 (reflecting cellular proliferation), vascular endothelial growth factor (VEGF) (the “endogenous marker” of tumor vessel growth), carbonic anhydrase (CAIX), hypoxia inducible transcription factor (HIF-1α), and human papillomavirus (HPV). Additionally, necrosis was estimated based on H&E staining. The Spearman correlation was used to compare DCE-MRI, 1H-MRS, and molecular marker data.
A significant correlation was observed between DCE-MRI parameter std(kep) and VEGF IHC expression level (rho = 0.81, p = 0.0001). Furthermore, IHC expression levels of Ki-67 inversely correlated with std(Ktrans) and std(ve) (rho = −0.71; p = 0.004, and rho = −0.73; p = 0.003, respectively). Other DCE-MRI, 1H-MRS and IHC values did not show significant correlation.
The results of this preliminary study indicate that the level of heterogeneity of perfusion in metastatic HNSCC seems positively correlated with angiogenesis, and inversely correlated with proliferation. These results are preliminary in nature and are indicative, and not definitive, trends portrayed in HNSCC patients with nodal disease. Future studies with larger patient populations need to be carried out to validate and clarify our preliminary findings.
PMCID: PMC3368067  PMID: 22366441
Head and neck squamous cell carcinoma; 1H-MRS; DCE-MRI; molecular markers
4.  Phase II Study of Saracatinib (AZD0530) for Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) 
Anticancer research  2011;31(1):249-253.
Saracatinib (AZD0530) is an orally available Src kinase inhibitor. A phase II study was conducted to evaluate saracatinib in patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC).
Patients and Methods
This was an open-label, single-arm, phase II study. Patients received 175 mg saracatinib daily either orally or by percutaneous gastrostomy tube. Radiologic imaging for response was planned at the end of each eight-week cycle.
Nine patients were enrolled. All patients had received prior radiotherapy and six patients had received prior chemotherapy for recurrent or metastatic disease. The most common adverse event was fatigue. Eight patients had progression of disease by response evaluation criteria in solid tumors (RECIST) within the first eight-week cycle and one patient was removed from the study after 11 days due to clinical decline with stable disease according to the RECIST criteria. Median overall survival was six months. The study was closed early due to lack of efficacy according to the early stopping rule.
Single-agent saracatinib does not merit further study in recurrent or metastatic HNSCC.
PMCID: PMC3705960  PMID: 21273606
HNSCC; phase II; Src; AZD0530; saracatinib
5.  Craniofacial Surgery for Esthesioneuroblastoma: Report of an International Collaborative Study 
Introduction Impact of treatment and prognostic indicators of outcome are relatively ill-defined in esthesioneuroblastomas (ENB) because of the rarity of these tumors. This study was undertaken to assess the impact of craniofacial resection (CFR) on outcome of ENB.
Patients and Methods Data on 151 patients who underwent CFR for ENB were collected from 17 institutions that participated in an international collaborative study. Patient, tumor, treatment, and outcome data were collected by questionnaires and variables were analyzed for prognostic impact on overall, disease-specific and recurrence-free survival. The majority of tumors were staged Kadish stage C (116 or 77%). Overall, 90 patients (60%) had received treatment before CFR, radiation therapy in 51 (34%), and chemotherapy in 23 (15%). The margins of surgical resection were reported positive in 23 (15%) patients. Adjuvant postoperative radiation therapy was used in 51 (34%) and chemotherapy in 9 (6%) patients.
Results Treatment-related complications were reported in 49 (32%) patients. With a median follow-up of 56 months, the 5-year overall, disease-specific, and recurrence-free survival rates were 78, 83, and 64%, respectively. Intracranial extension of the disease and positive surgical margins were independent predictors of worse overall, disease-specific, and recurrence-free survival on multivariate analysis.
Conclusion This collaborative study of patients treated at various institutions across the world demonstrates the efficacy of CFR for ENB. Intracranial extension of disease and complete surgical excision were independent prognostic predictors of outcome.
PMCID: PMC3424016  PMID: 23730550
nose neoplasms/mortality/pathology/surgery/*therapy; esthesioneuroblastoma; olfactory/*therapy; combined modality therapy; radiotherapy; adjuvant; survival analysis
6.  Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a Predictor of Outcome in Head and Neck Squamous Cell Carcinoma Patients with Nodal Metastases 
Dynamic contrast-enhanced-MRI (DCE-MRI) can provide information regarding tumor perfusion and permeability and has shown prognostic value in certain tumors types. The goal of the present study was to assess the prognostic value of pretreatment DCE-MRI in head and neck squamous cell carcinoma (HNSCC) patients with nodal disease undergoing chemoradiation therapy or surgery.
Methods and Materials
Seventy-four patients with histologically proven squamous cell carcinoma and neck nodal metastases were eligible for the study. Pretreatment DCE-MRI was performed on a 1.5T MRI. Clinical follow-up was a minimum of 12 months. DCE-MRI data were analyzed using Tofts model. DCE-MRI parameters were related to treatment outcome (progression free survival [PFS] and overall survival [OS]). Patients were grouped as no evidence of disease (NED), alive with disease (AWD), dead with disease (DOD) or dead of other causes (DOC). Prognostic significance was assessed using the log rank test for single variables and Cox proportional hazards regression for combinations of variables.
At last clinical follow-up, for stage III, all 12 pts were NED, for stage IV, 43 patients were NED, 4 were AWD, 11 were DOD, and 4 were DOC. Ktrans is volume transfer constant. In a stepwise Cox regression skewness of Ktrans was the strongest predictor for stage IV patients (PFS and OS: p<0.001).
Our study shows that skewness of Ktrans was the strongest predictor of PFS and OS in stage IV HNSCC patients with nodal disease. This study suggests an important role for pretreatment DCE-MRI parameter Ktrans as a predictor of outcome in these patients.
PMCID: PMC3177034  PMID: 21601373
Dynamic Contrast Enhanced-MRI (DCE-MRI); head and neck squamous cell carcinoma (HNSCC); volume transfer constant (Ktrans)
7.  Tumor Metabolism and Perfusion in Head and Neck Squamous Cell Carcinoma: Pretreatment Multimodality Imaging with 1H-Magnetic Resonance Spectroscopy, Dynamic Contrast-Enhanced MRI and 18F-FDG PET 
To correlate proton magnetic resonance spectroscopy (1H-MRS), dynamic contrast-enhanced MRI (DCE-MRI) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in nodal metastases of patients with head and neck squamous cell carcinoma (HNSCC) for assessment of tumor biology. Additionally, pretreatment multimodality imaging (MMI) was evaluated for its efficacy in predicting short-term response to treatment.
Methods and Materials
Metastatic neck nodes were imaged with 1H-MRS, DCE-MRI and 18F-FDG PET in 16 patients with newly diagnosed HNSCC before treatment. Short-term radiological response was evaluated at 3–4 months. The correlations between 1H-MRS (choline concentration, Cho/W), DCE-MRI (volume transfer constant, Ktrans; volume fraction of the extravascular extracellular space, ve; and redistribution rate constant, kep) and 18F-FDG PET (standard uptake value, SUV; and total lesion glycolysis, TLG) were calculated using non-parametric Spearman rank correlation. To predict the short-term response, logistic regression analysis was performed.
A significant positive correlation was found between Cho/W and TLG (ρ = 0.599, p = 0.031). Cho/W correlated negatively with heterogeneity measures std(ve) (ρ = −0.691, p = 0.004) and std(kep) (ρ = −0.704, p = 0.003). SUVmax values correlated strongly with MRI tumor volume (ρ = 0.643, p = 0.007). Logistic regression indicated that std(Ktrans) and SUVmean were significant predictors of short-term response (p < 0.07).
Pretreatment multi-modality imaging using 1H-MRS, DCE-MRI and 18F-FDG PET is feasible in HNSCC patients with nodal metastases. Additionally, combined DCE-MRI and 18F-FDG PET parameters were predictive of short-term response to treatment.
PMCID: PMC3137671  PMID: 21236594
Head and neck squamous cell carcinoma; 1H-MRS; DCE-MRI; 18F-FDG PET; short-term treatment response
8.  Noninvasive assessment of tumor microenvironment using dynamic contrast enhanced MRI and 18F- fluoromisonidazole PET imaging in neck nodal metastases 
Pretreatment multimodality imaging can provide useful anatomical and functional data about tumors, including perfusion and possibly hypoxia status. The purpose of our study was to assess non-invasively the tumor microenvironment of neck nodal metastases in patients with head and neck (HN) cancer by investigating the relationship between tumor perfusion measured using Dynamic Contrast Enhanced MRI (DCE-MRI) and hypoxia measured by 18F-fluoromisonidazole (18F-FMISO) PET.
Methods and Materials
Thirteen newly diagnosed HN cancer patients with metastatic neck nodes underwent DCE-MRI and 18F-FMISO PET imaging prior to chemotherapy and radiation therapy. The matched regions of interests from both modalities were analyzed. To examine the correlations between DCE-MRI parameters and standard uptake value (SUV) measurements from 18F-FMISO PET, the non-parametric Spearman correlation coefficient was calculated. Furthermore, DCE-MRI parameters were compared between nodes with 18F-FMISO uptake and nodes with no 18F-FMISO uptake using Mann-Whitney U tests.
For the 13 patients, a total of 18 nodes were analyzed. The nodal size strongly correlated with the 18F-FMISO SUV (ρ=0.74, p<0.001). There was a strong negative correlation between the median kep (ρ=−0.58, p=0.042) and the 18F-FMISO SUV. Hypoxic nodes (moderate to severe 18F-FMISO uptake) had significantly lower median Ktrans (p=0.049) and median kep (p=0.027) values than did non-hypoxic nodes (no 18F-FMISO uptake).
This initial evaluation of the preliminary results support the hypothesis that in metastatic neck lymph nodes, hypoxic nodes are poorly perfused (i.e., have significantly lower kep and Ktrans values) compared to non-hypoxic nodes.
PMCID: PMC2888682  PMID: 19906496
Dynamic Contrast Enhanced-MRI (DCE-MRI); 18F-fluoromisonidazole (FMISO) PET; 18F-fluorodeoxyglucose (FDG); head and neck (HN) cancer
9.  Functional Vagal Paraganglioma: A Case Report Illustrating Diagnosis and Management 
Skull Base  2010;20(6):491-496.
We report a case of functional vagal paraganglioma to illustrate the biochemical and radiological imaging tests important in diagnosis and to highlight the importance of a multidisciplinary team approach to manage the preoperative, perioperative, and postoperative effects of catecholamine secretion from these tumors.
PMCID: PMC3134809  PMID: 21772811
Paraganglioma; carotid body tumor; pheochromocytoma; glomas vagale
10.  Average arterial input function for quantitative dynamic contrast enhanced magnetic resonance imaging of neck nodal metastases 
The present study determines the feasibility of generating an average arterial input function (Avg-AIF) from a limited population of patients with neck nodal metastases to be used for pharmacokinetic modeling of dynamic contrast-enhanced MRI (DCE-MRI) data in clinical trials of larger populations.
Twenty patients (mean age 50 years [range 27–77 years]) with neck nodal metastases underwent pretreatment DCE-MRI studies with a temporal resolution of 3.75 to 7.5 sec on a 1.5T clinical MRI scanner. Eleven individual AIFs (Ind-AIFs) met the criteria of expected enhancement pattern and were used to generate Avg-AIF. Tofts model was used to calculate pharmacokinetic DCE-MRI parameters. Bland-Altman plots and paired Student t-tests were used to describe significant differences between the pharmacokinetic parameters obtained from individual and average AIFs.
Ind-AIFs obtained from eleven patients were used to calculate the Avg-AIF. No overall significant difference (bias) was observed for the transfer constant (Ktrans) measured with Ind-AIFs compared to Avg-AIF (p = 0.20 for region-of-interest (ROI) analysis and p = 0.18 for histogram median analysis). Similarly, no overall significant difference was observed for interstitial fluid space volume fraction (ve) measured with Ind-AIFs compared to Avg-AIF (p = 0.48 for ROI analysis and p = 0.93 for histogram median analysis). However, the Bland-Altman plot suggests that as Ktrans increases, the Ind-AIF estimates tend to become proportionally higher than the Avg-AIF estimates.
We found no statistically significant overall bias in Ktrans or ve estimates derived from Avg-AIF, generated from a limited population, as compared with Ind-AIFs.
However, further study is needed to determine whether calibration is needed across the range of Ktrans. The Avg-AIF obtained from a limited population may be used for pharmacokinetic modeling of DCE-MRI data in larger population studies with neck nodal metastases. Further validation of the Avg-AIF approach with a larger population and in multiple regions is desirable.
PMCID: PMC2679707  PMID: 19351382

Results 1-10 (10)