Distinguishing Intrathyroid Parathyroid Adenoma from Colloid Nodules and Papillary Thyroid Carcinomas Using Multiphasic Multidetector Computed Tomography.

OBJECTIVE: The aim of the study is to determine whether multiphase multidetector computed tomography (4D-MDCT) can differentiate between intrathyroid parathyroid adenomas (ITPAs), colloid nodules, and papillary thyroid carcinoma (PTC). METHODS: We studied 22 ITPAs, 22 colloid nodules, and 11 PTCs in 55 patients. Hounsfield unit (HU) values of the nodules were measured on 4D-MDCT in the precontrast, arterial, venous, and delayed phases. Raw HU values, phase with peak enhancement, and washout percentages between the phases were evaluated. RESULTS: Regardless of size, all ITPAs (22/22) showed peak enhancement in the arterial phase, which was significantly greater than both colloid nodules (15/22) and PTC (6/11, P = 0.002); thus, nodules with peak enhancement in the venous or delayed phase were not ITPAs (specificity = 1). For nodules with peak enhancement in the arterial phase, the percentage washout in the arterial-to-venous phases separated ITPAs from PTC and colloid nodules (P < 0.001) with greater than or equal to 23.95% loss of HU value implying IPTA (area under curve, 0.79). This left a subset of colloid nodules or PTC that either peaked in the venous or delayed phase or had an arterial-to-venous phase washout of less than 23.95%. From this subset, PTC measuring 1 cm or greater could be separated from colloid based on HU values in the arterial phase with a cutoff HU value less than 81.4 for PTC (area under curve, 0.72) and an HU value greater than 164.5 suggested colloid. CONCLUSIONS: Intrathyroid parathyroid adenomas can be distinguished from colloid nodules and PTC by peak enhancement in the arterial phase and rapid washout. A subset of colloid and PTC measuring 1 cm or greater can be separated using arterial phase HU values.

Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial.

BACKGROUND: After brain metastasis resection, whole brain radiotherapy decreases local recurrence, but might cause cognitive decline. We did this study to determine if stereotactic radiosurgery (SRS) to the surgical cavity improved time to local recurrence compared with that for surgical resection alone. METHODS: In this randomised, controlled, phase 3 trial, we recruited patients at a single tertiary cancer centre in the USA. Eligible patients were older than 3 years, had a Karnofsky Performance Score of 70 or higher, were able to have an MRI scan, and had a complete resection of one to three brain metastases (with a maximum diameter of the resection cavity ≤4 cm). Patients were randomly assigned (1:1) with a block size of four to either SRS of the resection cavity (within 30 days of surgery) or observation. Patients were stratified by histology of the primary tumour, metastatic tumour size, and number of metastases. The primary endpoint was time to local recurrence in the resection cavity, assessed by blinded central review of brain MRI scans by the study neuroradiologist in the modified intention-to-treat population that analysed patients by randomised allocation but excluded patients found ineligible after randomisation. Participants and other members of the treatment team (excluding the neuroradiologist) were not masked to treatment allocation. The trial is registered with ClinicalTrials.gov, number NCT00950001, and is closed to new participants. FINDINGS: Between Aug 13, 2009, and Feb 16, 2016, 132 patients were randomly assigned to the observation group (n=68) or SRS group (n=64), with 128 patients available for analysis; four patients were ineligible (three from the SRS group and one from the observation group). Median follow-up was 11·1 months (IQR 4·8-20·4). 12-month freedom from local recurrence was 43% (95% CI 31-59) in the observation group and 72% (60-87) in the SRS group (hazard ratio 0·46 [95% CI 0·24-0·88]; p=0·015). There were no adverse events or treatment-related deaths in either group. INTERPRETATION: SRS of the surgical cavity in patients who have had complete resection of one, two, or three brain metastases significantly lowers local recurrence compared with that noted for observation alone. Thus, the use of SRS after brain metastasis resection could be an alternative to whole-brain radiotherapy. FUNDING: National Institutes of Health.

Management of the lymph node-positive neck in the patient with human papillomavirus-associated oropharyngeal cancer.

BACKGROUND: The goal of the current study was to assess the rates of recurrence in the neck for patients with lymph node-positive human papillomavirus-associated cancer of the oropharynx who were treated with definitive radiotherapy (with or without chemotherapy). METHODS: This is a single-institution retrospective study. Methodology included database search, and statistical testing including frequency analysis, Kaplan-Meier tests, and comparative tests including chi-square, logistic regression, and log-rank. RESULTS: The cohort consisted of 401 patients with lymph node-positive disease who underwent radiotherapy between January 2006 and June 2012. A total of 388 patients had computed tomography restaging, and 251 had positron emission tomography and/or ultrasound as a component of their postradiation staging. Eighty patients (20%) underwent neck dissection, and 21 patients (26%) had a positive specimen. The rate of neck dissection increased with increasing lymph node stage, and was lower in patients who had positron emission tomography scans or ultrasound in addition to computed tomography restaging. The median follow-up was 30 months. The 2-year actuarial neck recurrence rate was 7% and 5%, respectively, in all patients and those with local control. Lymph node recurrence rates were greater in current smokers (P = .008). There was no difference in lymph node recurrence rates noted between patients who did and those who did not undergo a neck dissection (P = .4) CONCLUSIONS: A treatment strategy of (chemo)radiation with neck dissection performed based on response resulted in high rates of regional disease control in patients with human papillomavirus-associated oropharyngeal cancer.

CT findings in temporal bone osteoradionecrosis.

PURPOSE: The goal of this study was to describe computed tomographic findings in patients with clinically proven temporal bone (TB) osteoradionecrosis (ORN) (TB-ORN). MATERIALS AND METHODS: Computed tomographic scans of 20 patients were retrospectively evaluated for bony and soft tissue abnormalities. Clinical severity was graded based on level of therapy administered: mild (observation), moderate (antibiotics/hyperbaric oxygen), or severe (surgery). RESULTS: Radiation dose to the primary tumor ranged from 30 to 75.6 Gy. Time to onset of ORN from completion of radiation therapy was 2 to 22 years (median, 7 years). CLINICAL FINDINGS: exposed bone, 20 of the 20 patients; otorrhea, 17 of the 20 patients; hearing loss, 11 of the 20 patients; otalgia, 10 of the 20 patients; facial nerve paralysis, 2 of the 20 patients; gait imbalance, 2 of the 20 patients. Computed tomographic findings: external auditory canal erosions, 18 of the 20 patients; mastoid effusion, 18 of the 20 patients; mastoid bony coalescence, 5 of the 20 patients; enhancing soft tissue, 6 of the 20 patients; soft tissue gas, 6 of the 20 patients; temporomandibular joint/condylar erosion, 3 of the 20 patients.Three patients developed an abscess. CONCLUSION: Mastoid effusion and external auditory canal erosions are commonly seen with TB-ORN. Clinically moderate or severe cases of TB-ORN are more likely to demonstrate enhancing soft tissue (P = 0.002), soft tissue gas (P = 0.002), and temporomandibular joint involvement (P = 0.07).

Change in postsurgical cavity size within the first 30 days correlates with extent of surrounding edema: consequences for postoperative radiosurgery.

OBJECTIVE: Resection cavity diameter of less than 40 mm is required to be eligible for stereotactic radiosurgery (SRS), after gross total resection of brain metastasis at our institution. Our study evaluates the correlation between vasogenic edema and change in cavity size for 30 days. METHODS: Cavity size was measured on the postoperative and follow-up magnetic resonance imaging. Vasogenic edema was quantified as the largest axial measurement of T2 hyperintensity surrounding the resection cavity (postoperative magnetic resonance imaging). RESULTS: Thirty-nine resection cavities (37 patients) were reviewed. There was a statistically significant (Pearson coefficient = -0.35; P = 0.02) negative correlation between edema and change in cavity size. An arbitrary cutoff value of a 15-mm edema yielded a sensitivity of 96% and a specificity of 65% (P < 0.001) to predict 10% decrease in cavity size. CONCLUSIONS: In patients with cavity size close to the size cutoff for SRS, rescanning closer to the date of SRS should be considered, especially if there is significant edema surrounding the cavity.

Graves' Eye Disease: Clinical and Radiological Diagnosis.

Graves' disease is an autoimmune disorder in which hyperthyroidism results in various systematic symptoms, with about 30% of patients presenting with Graves' eye disease (GED). The majority of patients with GED develop mild symptoms, including eyelid retraction, exposure of the globe, superior rectus-levator muscle complex inflammation, and fat expansion, leading to exophthalmos. More severe cases can result in extraocular muscle enlargement, restricted ocular movement, eyelid and conjunctival edema, and compression of the optic nerve leading to compressive optic neuropathy (CON). GED severity can be classified using the Clinical Activity Score, European Group on Graves' Orbitopathy scale, NO SPECS Classification system, and VISA system. CT and MRI aid in the diagnosis of GED through the demonstration of orbital pathology. Several recent studies have shown that MRI findings correlate with disease severity and can be used to evaluate CON. Mild cases of GED can be self-limiting, and patients often recover spontaneously within 2-5 years. When medical treatment is required, immunomodulators or radiotherapy can be used to limit immunologic damage. Surgery may be needed to improve patient comfort, preserve the orbit, and prevent vision loss from optic nerve compression or breakdown of the cornea.

Imaging characteristics of hyperfunctioning parathyroid adenomas using multiphase multidectector computed tomography: a quantitative and qualitative approach.

OBJECTIVE: The objective of the study was to characterize the enhancement pattern of hyperfunctioning parathyroid adenomas on multiphase multidetector computed tomography (CT) or 4-dimensional CT. METHODS: We retrospectively studied the enhancement patterns of 48 pathologically confirmed parathyroid adenomas with 4-dimensional CT, compliant with institutional review and the Health Insurance Portability and Accountability Act. Region-of-interest analysis was done at baseline and at arterial (25 seconds), venous (55 seconds), and delayed (85 seconds) enhancement phases over the adenoma and adjacent normal thyroid tissue. Qualitative and quantitative analysis was done. Discriminant functions were calculated using a multivariate logistic regression model, and receiver operating characteristic curves were measured. RESULTS: Adenomas are lower than thyroid in density, demonstrate avid early contrast enhancement, and show rapid wash-out of contrast. Adenomas and thyroid had baseline Hounsfield unit attenuations of 35 ± 11 and 94 ± 21 and enhancement percentage change from baseline to arterial of 493% ± 328% and 132% ± 148%, respectively (P < 0.0001 both). Quantitative analysis showed that these 2 measures of baseline density and the percentage change from baseline to arterial were the most powerful discriminatory features, with contrast wash-out from arterial peak to venous phase being a less powerful discriminator. Several discriminant functions were derived, the best of which was: X = 13.74 - (0.207 × baseline Hounsfield unit) - (0.006 × percent density change from baseline to arterial). X > 0.2 classifies tissue as parathyroid with high certainty (area under the receiver operating characteristic curve = 0.98; specificity, 0.938; sensitivity, 0.999). CONCLUSIONS: Parathyroid adenomas have a characteristic enhancement pattern that can be distinguished from thyroid tissue: the key diagnostic discriminators are baseline density, percentage change in density from baseline to arterial enhancement, and percentage decrease in density from arterial to venous phases.

Management of Anaplastic and Recurrent Differentiated Thyroid Cancer: Indications for Surgical Resection, Molecular Testing, and Systemic Therapy.

Differentiated and anaplastic thyroid cancer are tumors derived from follicular thyroid cancers and are clinically and genetically distinct. Treatment of these tumors has evolved over the past decade, with 6 drugs/drug combinations that are US Food and Drug Administration approved.

Imaging of the Thyroid: Practical Approach.

Imaging evaluation of the thyroid gland spans a plethora of modalities, including ultrasound imaging, cross-sectional studies, and nuclear medicine techniques. The overlapping of clinical and imaging findings of benign and malignant thyroid disease can make interpretation a complex undertaking. We aim to review and simplify the vast current literature and provide a practical approach to the imaging of thyroid disease for application in daily practice. Our approach highlights the keys to differentiating and diagnosing common benign and malignant disease affecting the thyroid gland.

Imaging of Cervical Lymph Nodes in Thyroid Cancer: Ultrasound and Computed Tomography.

Sonographic evaluation of cervical lymph nodes in patients with thyroid malignancy is important both for preoperative staging and for post-treatment surveillance, and contrast-enhanced computed tomography plays a complementary role. Knowledge of anatomy and surgical approaches, combined with an understanding of the various imaging features that distinguish malignant from benign lymph nodes, allows for accurate staging, thereby enabling complete surgical initial resection.

Using the American College of Radiology Thyroid Imaging Reporting and Data System at the Point of Care: Sonographer Performance and Interobserver Variability.

The purpose of this study was to assess inter-observer variability and performance when sonographers assign features to thyroid nodules on ultrasound using the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS). Fifteen sonographers retrospectively evaluated 100 thyroid nodules and assigned features to each nodule according to ACR TI-RADS lexicon. Ratings were compared with one another and to a gold standard using Fleiss' and Cohen's kappa statistics, respectively. Sonographers were also asked subjective questions regarding their comfort level assessing each feature, and opinions were compared with performance using a mixed effects model. Sonographers demonstrated only slight agreement for margin (κ = 0.18, 95% confidence interval [CI]: 0.16-0.20) and large comet tail artifact (κ = 0.08, 95% CI: 0.06-0.10) but better performance for macrocalcification (κ = 0.41, 95% CI: 0.39-0.43) and no echogenic foci (κ = 0.52, 95% CI: 0.50-0.54). Sonographer comfort level with different feature assignments did not statistically correlate with performance for a given feature. In conclusion, sonographers using ACR TI-RADS to assign thyroid nodule features on ultrasound demonstrate a range of agreement across features, with margin and large comet tail artifact showing the most variability. These results highlight potential areas of focus for sonographer education efforts as ACR TI-RADS continues to be implemented in radiology departments.

Primary Malignant Thyroid Teratoma: An Institutional Experience.

BACKGROUND: Primary malignant thyroid teratomas are very rare tumors (fewer than 35 previously reported cases in the literature) typically affecting young adult women. While prognosis is poor, there have been some reports of successful treatment regimens. Four cases treated successfully are reported, and a review of the existing literature is provided. PATIENT FINDINGS: Medical records of four patients with histopathologically confirmed malignant thyroid teratomas treated at the University of Texas MD Anderson Cancer Center between 1994 and 2017 were reviewed. The patients were treated with variable treatment regimens consisting of surgical excision with or without aggressive combination chemotherapy (bleomycin, etoposide, and cisplatin; cyclophasphamide, adriamycin, and cisplatin; actinomycin-D, cyclophosphamide, and etoposide; bleomycin, vincristine, and cisplatin; or vincristine, methotrexate, bleomycin, and cisplatin). SUMMARY: All four patients were young women <40 years of age. One patient had thyroid surgery alone, another had surgery with postoperative adjuvant chemotherapy, and two patients underwent neoadjuvant chemotherapy with significant tumor regression prior to definitive thyroid surgery. No patients had postoperative radiation therapy. All patients remained alive and disease free a median of 172 months (range 52-282 months) following completion of therapy. CONCLUSIONS: This case series represents the largest and longest follow-up from a single institution in the literature to date on primary malignant thyroid teratomas. Based on the existing literature and the authors' experience with these four patients, it is suggested that neoadjuvant chemotherapy combined with surgical excision is a promising approach for patients with gross extrathyroidal extension, cervical lymph node metastases, and/or distantly metastatic disease.

Vascular flow on doppler sonography may not be a valid characteristic to distinguish colloid nodules from papillary thyroid carcinoma even when accounting for nodular size.

BACKGROUND: The purpose of this study was to test the hypothesis that there is no significant difference in vascular flow patterns between cytopathologically-proven colloid nodules and papillary thyroid carcinoma (PTC) even when adjusting for nodule size. METHODS: Doppler vascular flow patterns in 200 colloid nodules and 166 nodules with PTC were retrospective reviewed independently by 2 neuroradiologists blinded to the cytopathological results. Absence of vascular flow, perinodular and/or intranodular flow, and diffuse vascular flow were recorded. The vascular flow patterns were compared without (Fisher exact test) and with (Kruskal-Wallis test) an adjustment for nodular size. Using the most common flow pattern as the reference group, multiple logistic regression was used to compare the flow patterns. Sample skewness was calculated to determine degree of symmetry of the size distribution for each vascular flow category. RESULTS: No significant difference was found in the tested vascular flow patterns between colloid nodules and PTC both without and with an adjustment for nodular size (P>0.05). Intranodular flow only was the largest group (n=111/366) and used as the reference for multiple logistic regression. No significant difference was noted between the vascular flow patterns (P>0.05). Sample skewness showed that nodules were generally smaller in size with outliers of larger size on the opposite end of the spectrum. CONCLUSIONS: Independent of nodule size the absence or presence of vascular flow is not significantly different between colloid nodules and PTC. Therefore, vascular flow may not be useful in distinguishing between colloid nodules and PTC.

Complete Surgical Resection Following Neoadjuvant Dabrafenib Plus Trametinib in BRAFV600E-Mutated Anaplastic Thyroid Carcinoma.

Background: When achieved, complete surgical resection improves outcomes in anaplastic thyroid carcinoma (ATC). However, most ATC patients present with advanced inoperable disease, often with impending airway obstruction, increased hemorrhage risk, and significant dysphagia. Novel treatment strategies are critically needed to improve disease control and decrease locoregional morbidity. The objective of this study was to determine the feasibility and effectiveness of a neoadjuvant regimen by using dabrafenib with trametinib followed by surgical resection in patients with initially unresectable BRAFV600E-mutated ATC. Methods: Case series of six consecutive patients with BRAFV600E-mutated ATC diagnosed between January 2017 and February 2018. Pathologic confirmation of ATC was obtained before treatment. BRAFV600E status was ascertained via immunohistochemistry or sequencing of circulating tumor DNA. All patients received dabrafenib and trametinib (DT) followed by surgical resection and adjuvant chemoradiation. Three patients also received pembrolizumab. Results: Complete surgical resection was achieved in all patients. Histopathologic analyses of resected specimens showed high pathologic response rates with significantly decreased ATC viability and residual papillary thyroid carcinoma components. Overall survival at six months and one year was 100% and 83%, respectively. Locoregional control rate was 100%. Two patients died of distant metastases without evidence of locoregional disease at 8 and 14 months from diagnosis. The remaining four patients had no evidence of disease at the last follow-up. Conclusions: We report the first series in the literature of BRAFV600E-mutated ATC patients with locoregionally advanced disease treated with DT followed by surgical resection. We demonstrated feasibility of complete resection, decreased need for tracheostomy, high pathologic response rates, and durable locoregional control with symptom amelioration.

Neoadjuvant BRAF- and Immune-Directed Therapy for Anaplastic Thyroid Carcinoma.

Anaplastic thyroid cancer (ATC) is a devastating disease with a dismal prognosis. Patients who have disease confined to the thyroid and who are able to undergo complete surgery and chemoradiation stand the best chance for survival. Unfortunately, nearly 50% of patients have distant metastases at diagnosis, and most present with locally advanced, unresectable tumors. Nevertheless, BRAF-mutated ATC patients represent a subset of cases who can benefit from a combination therapy with BRAF and MEK inhibitors. Here, a patient is presented with end-stage, locally advanced, unresectable ATC who was treated with this combination. Immunotherapy with pembrolizumab was added at the first sign of progression after which he achieved a partial response to therapy, enabling a complete surgical resection followed by postoperative chemoradiation to be undertaken. This novel neoadjuvant approach to BRAF-mutated ATC should be studied in further in clinical trials.

Tumor image-derived texture features are associated with CD3 T-cell infiltration status in glioblastoma.

This study analyzed magnetic resonance imaging (MRI) scans of Glioblastoma (GB) patients to develop an imaging-derived predictive model for assessing the extent of intratumoral CD3 T-cell infiltration. Pre-surgical T1-weighted post-contrast and T2-weighted Fluid-Attenuated-Inversion-Recovery (FLAIR) MRI scans, with corresponding mRNA expression of CD3D/E/G were obtained through The Cancer Genome Atlas (TCGA) for 79 GB patients. The tumor region was contoured and 86 image-derived features were extracted across the T1-post contrast and FLAIR images. Six imaging features-kurtosis, contrast, small zone size emphasis, low gray level zone size emphasis, high gray level zone size emphasis, small zone high gray level emphasis-were found associated with CD3 activity and used to build a predictive model for CD3 infiltration in an independent data set of 69 GB patients (using a 50-50 split for training and testing). For the training set, the image-based prediction model for CD3 infiltration achieved accuracy of 97.1% and area under the curve (AUC) of 0.993. For the test set, the model achieved accuracy of 76.5% and AUC of 0.847. This suggests a relationship between image-derived textural features and CD3 T-cell infiltration enabling the non-invasive inference of intratumoral CD3 T-cell infiltration in GB patients, with potential value for the radiological assessment of response to immune therapeutics.

Spatial habitats from multiparametric MR imaging are associated with signaling pathway activities and survival in glioblastoma.

Glioblastoma (GBM) show significant inter- and intra-tumoral heterogeneity, impacting response to treatment and overall survival time of 12-15 months. To study glioblastoma phenotypic heterogeneity, multi-parametric magnetic resonance images (MRI) of 85 glioblastoma patients from The Cancer Genome Atlas were analyzed to characterize tumor-derived spatial habitats for their relationship with outcome (overall survival) and to identify their molecular correlates (i.e., determine associated tumor signaling pathways correlated with imaging-derived habitat measurements). Tumor sub-regions based on four sequences (fluid attenuated inversion recovery, T1-weighted, post-contrast T1-weighted, and T2-weighted) were defined by automated segmentation. From relative intensity of pixels in the 3-dimensional tumor region, "imaging habitats" were identified and analyzed for their association to clinical and genetic data using survival modeling and Dirichlet regression, respectively. Sixteen distinct tumor sub-regions ("spatial imaging habitats") were derived, and those associated with overall survival (denoted "relevant" habitats) in glioblastoma patients were identified. Dirichlet regression implicated each relevant habitat with unique pathway alterations. Relevant habitats also had some pathways and cellular processes in common, including phosphorylation of STAT-1 and natural killer cell activity, consistent with cancer hallmarks. This work revealed clinical relevance of MRI-derived spatial habitats and their relationship with oncogenic molecular mechanisms in patients with GBM. Characterizing the associations between imaging-derived phenotypic measurements with the genomic and molecular characteristics of tumors can enable insights into tumor biology, further enabling the practice of personalized cancer treatment. The analytical framework and workflow demonstrated in this study are inherently scalable to multiple MR sequences.

The biopsy-proven benign thyroid nodule: is long-term follow-up necessary?

BACKGROUND: Thyroid nodules are common, and of those biopsied by fine-needle aspiration (FNA), the majority will be benign colloid nodules (BCN). Current guidelines suggest these BCN should be followed by ultrasonographic examination (US) every 3 years, with no endpoint specified. This study evaluated if long-term follow-up of benign thyroid nodules was associated with change in treatment or improvement in diagnosing a missed malignancy compared with short-term follow-up. STUDY DESIGN: All patients with FNA-based diagnosis of BCN at our institution from 1998 to 2009 were identified. Patients observed after the diagnosis were divided into short-term follow-up (<3 years) and long-term follow-up (≥3 years). Rates of repeat FNA, thyroidectomy, and malignancy detection were compared. RESULTS: Of 738 patients with BCN, 92 patients underwent thyroid resection after the initial US. Six hundred forty-six patients were observed, of which 366 returned for 1 or more follow-up US: 226 in the short-term group (median 13 months) and 140 in the long-term group (median 57 months). There were more follow-up US in long-term vs short-term (medians 4 vs 2, p < 0.01), more repeat FNAs in the long-term group (18 of 140 vs 8 of 226, p < 0.01); but no difference in interval thyroidectomies (13 of 140 vs 31 of 226, p = 0.25) or malignant final pathology (0 of 13 vs 2 of 31, p > 0.99). For all patients undergoing surgery, pathology was malignant in 2 of 136 (1.5%). CONCLUSIONS: Long-term follow-up of patients with BCN is associated with increased repeat FNA and US without improvement in the malignancy detection rate. After 3 years of follow-up, consideration should be given to ceasing long-term routine follow-up of biopsy-proven BCN.

Radiation-induced middle ear and mastoid opacification in skull base tumors treated with radiotherapy.

PURPOSE: To assess the incidence of middle ear (ME) pathology in patients treated with radiotherapy (RT) for skull base tumors. METHODS AND MATERIALS: A retrospective analysis of 61 patients treated with RT between 2003 and 2008 for skull base tumors was conducted. Clinical outcomes and demographics were reviewed. Dose-volume histogram analysis was performed on the eustachian canal (EC), ME, mastoid air cells, vestibular apparatus, cochlea, internal auditory canal, lateral and posterior nasopharynx, and temporal lobes to relate doses to symptoms and radiographic change. Otomastoid opacification was rated 0 (none), 1 (mild), 2 (moderate), and 3 (severe) by a neuroradiologist blinded to clinical outcomes and doses. RESULTS: The median prescribed dose was 50.4 Gy (range, 14-74 Gy). The ME mean dose was 14 Gy and 34 Gy for Grade 0-1 and 2-3 opacification, respectively (p<0.0001). The mean mastoid dose was 10 Gy and 26 Gy for Grade 0-1 and 2-3, respectively (p<0.0001). The mean EC dose was 17 Gy and 32 Gy for Grade 0-1 and 2-3, respectively (p=0.0001). Otomastoid opacification resolved in 17 of 40 patients (42.5%), at a mean of 17 months after RT (range, 2-45 months). Otomastoid opacification persisted in 23 of 40 patients (57.5%), with a mean follow-up of 23 months (range, 2-55 months). Multivariate analysis showed that mastoid dose>30 Gy (odds ratio=28.0, p<0.001) and posterior nasopharynx dose of >30 Gy (odds ratio=4.9, p=0.009) were associated with Grade 2-3 effusions, whereas other factors including dose to EC and ME were not significant. CONCLUSIONS: A mean RT dose>30 Gy to the mastoid air cells or posterior nasopharynx is associated with increased risk of moderate to severe otomastoid opacification, which persisted in more than half of patients at 2-year follow-up.