Hilda E. Stambuk

Sensorineural hearing loss in combined modality treatment of nasopharyngeal carcinoma.

Combined modality therapy has become the standard of care for nasopharyngeal carcinoma, yet the combined ototoxic effects of radiation and cisplatin are poorly understood. The incidence and severity of sensorineural hearing loss (SNHL) with combined modality therapy was evaluated and the dose–response relation between radiation and hearing loss was investigated.

Noninvasive Assessment of Tumor Microenvironment Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging and 18F-Fluoromisonidazole Positron Emission Tomography Imaging in Neck Nodal Metastases

PURPOSE To assess noninvasively the tumor microenvironment of neck nodal metastases in patients with head-and-neck cancer by investigating the relationship between tumor perfusion measured using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and hypoxia measured by (18)F-fluoromisonidazole ((18)F-FMISO) positron emission tomography (PET). METHODS AND MATERIALS Thirteen newly diagnosed head-and-neck cancer patients with metastatic neck nodes underwent DCE-MRI and (18)F-FMISO PET imaging before chemotherapy and radiotherapy. 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 (18)F-FMISO PET, the nonparametric Spearman correlation coefficient was calculated. Furthermore, DCE-MRI parameters were compared between nodes with (18)F-FMISO uptake and nodes with no (18)F-FMISO uptake using Mann-Whitney U tests. RESULTS For the 13 patients, a total of 18 nodes were analyzed. The nodal size strongly correlated with the (18)F-FMISO SUV (rho = 0.74, p < 0.001). There was a strong negative correlation between the median k(ep) (redistribution rate constant) value (rho = -0.58, p = 0.042) and the (18)F-FMISO SUV. Hypoxic nodes (moderate to severe (18)F-FMISO uptake) had significantly lower median K(trans) (volume transfer constant) (p = 0.049) and median k(ep) (p = 0.027) values than did nonhypoxic nodes (no (18)F-FMISO uptake). CONCLUSION 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 K(trans) and k(ep) values) compared with nonhypoxic nodes.

Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a Predictor of Outcome in Head-and-Neck Squamous Cell Carcinoma Patients With Nodal Metastases

PURPOSE 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 this 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 the 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. RESULTS At last clinical follow-up, for Stage III, all 12 patients were NED. For Stage IV, 43 patients were NED, 4 were AWD, 11 were DOD, and 4 were DOC. K(trans) is volume transfer constant. In a stepwise Cox regression, skewness of K(trans) (volume transfer constant) was the strongest predictor for Stage IV patients (PFS and OS: p <0.001). CONCLUSION Our study shows that skewness of K(trans) 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 K(trans) as a predictor of outcome in these patients.

Non-gaussian analysis of diffusion-weighted MR imaging in head and neck squamous cell carcinoma: A feasibility study.

BACKGROUND AND PURPOSE: Water in biological structures often displays non-Gaussian diffusion behavior. The objective of this study was to test the feasibility of non-Gaussian fitting by using the kurtosis model of the signal intensity decay curves obtained from DWI by using an extended range of b-values in studies of phantoms and HNSCC. MATERIALS AND METHODS: Seventeen patients with HNSCC underwent DWI by using 6 b-factors (0, 50–1500 s/mm2) at 1.5T. Monoexponential (yielding ADCmono) and non-Gaussian kurtosis (yielding apparent diffusion coefficient Dapp and apparent kurtosis coefficient Kapp) fits were performed on a voxel-by-voxel basis in selected regions of interest (primary tumors, metastatic lymph nodes, and spinal cord). DWI studies were also performed on phantoms containing either water or homogenized asparagus. To determine whether the kurtosis model provided a significantly better fit than did the monoexponential model, an F test was performed. Spearman correlation coefficients were calculated to assess correlations between Kapp and Dapp. RESULTS: The kurtosis model fit the experimental data points significantly better than did the monoexponential model (P < .05). Dapp was approximately twice the value of ADCmono (eg, in neck nodal metastases Dapp was 1.54 and ADCmono was 0.84). Kapp showed a weak Spearman correlation with Dapp in a homogenized asparagus phantom and for 44% of tumor lesions. CONCLUSIONS: The use of kurtosis modeling to fit DWI data acquired by using an extended b-value range in HNSCC is feasible and yields a significantly better fit of the data than does monoexponential modeling. It also provides an additional parameter, Kapp, potentially with added value.

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

PURPOSE To correlate proton magnetic resonance spectroscopy ((1)H-MRS), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and (18)F-labeled fluorodeoxyglucose positron emission tomography ([(18)F]FDG PET) of nodal metastases in patients with head and neck squamous cell carcinoma (HNSCC) for assessment of tumor biology. Additionally, pretreatment multimodality imaging was evaluated for its efficacy in predicting short-term response to treatment. METHODS AND MATERIALS Metastatic neck nodes were imaged with (1)H-MRS, DCE-MRI, and [(18)F]FDG PET in 16 patients with newly diagnosed HNSCC, before treatment. Short-term patient radiological response was evaluated at 3 to 4 months. Correlations among (1)H-MRS (choline concentration relative to water [Cho/W]), DCE-MRI (volume transfer constant [K(trans)]; volume fraction of the extravascular extracellular space [v(e)]; and redistribution rate constant [k(ep)]), and [(18)F]FDG PET (standard uptake value [SUV] and total lesion glycolysis [TLG]) were calculated using nonparametric Spearman rank correlation. To predict short-term responses, logistic regression analysis was performed. RESULTS A significant positive correlation was found between Cho/W and TLG (ρ = 0.599; p = 0.031). Cho/W correlated negatively with heterogeneity measures of standard deviation std(v(e)) (ρ = -0.691; p = 0.004) and std(k(ep)) (ρ = -0.704; p = 0.003). Maximum SUV (SUVmax) values correlated strongly with MRI tumor volume (ρ = 0.643; p = 0.007). Logistic regression indicated that std(K(trans)) and SUVmean were significant predictors of short-term response (p < 0.07). CONCLUSION Pretreatment multimodality imaging using (1)H-MRS, DCE-MRI, and [(18)F]FDG PET is feasible in HNSCC patients with nodal metastases. Additionally, combined DCE-MRI and [(18)F]FDG PET parameters were predictive of short-term response to treatment.

A phase 2 study of bevacizumab with cisplatin plus intensity‐modulated radiation therapy for stage III/IVB head and neck squamous cell cancer

For patients with stage III through IVB head and neck squamous cell carcinoma (HNSCC), concurrent high‐dose cisplatin plus radiation therapy is a widely accepted standard of care. HNSCC tumors that express high levels of vascular endothelial growth factor have been associated with a worse prognosis, and bevacizumab may sensitize tumors to cisplatin and radiation.

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.

Evaluation of different methods of 18F-FDG-PET target volume delineation in the radiotherapy of head and neck cancer.

Objective:To quantify differences between the alternative methods of 18F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET)-based delineation of the gross tumor volume in patients with head and neck cancer. Materials and Methods:Twelve patients with locally-advanced head and neck carcinomas were studied. The reference gross tumor volume (GTVref) was established by a radiation oncologist, along with a neuroradiologist, using the computed tomography-simulation and diagnostic magnetic resonance imaging data. With the GTVref obscured, a second radiation oncologist and a nuclear medicine physician determined the following contours: (1) high FDG uptake based on visual inspection (GTVvis), (2) the contour derived from the 50% maximum standardized uptake value (SUV) threshold (GTV50), (3) the contour derived from a 2.5 SUV absolute threshold (GTV2.5), and (4) the contours derived from an iterative segmentation algorithm (GTViter). These volumes were compared with the GTVref using a signed-ranks test with the exact reference distribution. Results:The average GTVref was 75.5 mL (median 72.8 mL, range 22.2–138.4 mL). The average GTVvis was 57.6 (median 55.4 mL, range 12–115.8 mL). Overall, a 21% reduction in volume size was observed with GTVvis versus GTVref. When the signed-ranks test with the exact reference distribution was applied, the difference was not statistically significant (P = 0.32). The average GTV2.5 was 60 mL (median 64.5, range 8.8–90.3 mL). The differences between GTV2.5 and GTVref were not statistically significant (P = 0.35). The use of GTV50 and GTViter produced significantly smaller volumes with respect to GTVref (P < 0.005). Conclusions:PET-based tumor volumes are strongly affected by the choice of threshold level. Quantitatively, GTVs derived from visual inspection of the region of high FDG uptake do not significantly differ from GTVref in this cohort of patients. The inclusion of alternative FDG-PET segmentation data, other than visual inspection, may reduce target volumes significantly.

Average arterial input function for quantitative dynamic contrast enhanced magnetic resonance imaging of neck nodal metastases

BackgroundThe 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.MethodsTwenty 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.ResultsInd-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.ConclusionWe 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.

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.