University of Washington Quality of Life subdomain outcomes after treatment of sinonasal malignancy: A prospective, multicenter study.

PURPOSE: Sinonasal malignancies (SNMs) adversely impact patients' quality of life (QOL) and are frequently identified at an advanced stage. Because these tumors are rare, there are few studies that examine the specific QOL areas that are impacted. This knowledge would help improve the care of these patients. METHODS: In this prospective, multi-institutional study, 273 patients with SNMs who underwent definitive treatment with curative intent were evaluated. We used the University of Washington Quality of Life (UWQOL) instrument over 5 years from diagnosis to identify demographic, treatment, and disease-related factors that influence each of the 12 UWQOL subdomains from baseline to 5 -years post-treatment. RESULTS: Multivariate models found endoscopic resection predicted improved pain (vs. nonsurgical treatment CI 2.4, 19.4, p = 0.01) and appearance versus open (CI 27.0, 35.0, p < 0.001) or combined (CI 10.4, 17.1, p < 0.001). Pterygopalatine fossa involvement predicted worse swallow (CI -10.8, -2.4, p = 0.01) and pain (CI -17.0, -4.0, p < 0.001). Neck dissection predicted worse swallow (CI -14.8, -2.8, p < 0.001), taste (CI -31.7, -1.5, p = 0.02), and salivary symptoms (CI -28.4, -8.6, p < 0.001). Maxillary involvement predicted worse chewing (CI 9.8, 33.2; p < 0.001) and speech (CI -21.8, -5.4, p < 0.001) relative to other sites. Advanced T stage predicted worse anxiety (CI -13.0, -2.0, p = 0.03). CONCLUSIONS: Surgical approach, management of cervical disease, tumor extent, and site of involvement impacted variable UWQOL symptom areas. Endoscopic resection predicted better pain, appearance, and chewing compared with open. These results may aid in counseling patients regarding potential QOL expectations in their SNM treatment and recovery course.

68 Ga-DOTATATE PET to Characterize Lesions in the Neuroaxis.

AIM: The differentiation of paragangliomas, schwannomas, meningiomas, and other neuroaxis tumors in the head and neck remains difficult when conventional MRI is inconclusive. This study assesses the utility of 68 Ga-DOTATATE PET/CT as an adjunct to hone the diagnosis. PATIENTS AND METHODS: This retrospective study considered 70 neuroaxis lesions in 52 patients with 68 Ga-DOTATATE PET/CT examinations; 22 lesions (31%) had pathologic confirmation. Lesions were grouped based on pathological diagnosis and best radiologic diagnosis when pathology was not available. Wilcoxon rank sum tests were used to test for differences in SUV max among paragangliomas, schwannomas, and meningiomas. Receiver operator characteristic curves were constructed. RESULTS: Paragangliomas had a significantly greater 68 Ga-DOTATATE uptake (median SUV max , 62; interquartile range [IQR], 89) than nonparagangliomas. Schwannomas had near-zero 68 Ga-DOTATATE uptake (median SUV max , 2; IQR, 1). Intermediate 68 Ga-DOTATATE uptake was seen for meningiomas (median SUV max , 19; IQR, 6) and other neuroaxis lesions (median SUV max , 7; IQR, 9). Receiver operator characteristic analysis demonstrated an area under the curve of 0.87 for paragangliomas versus all other lesions and 0.97 for schwannomas versus all other lesions. CONCLUSIONS: Marked 68 Ga-DOTATATE uptake (>50 SUV max ) favors a diagnosis of paraganglioma, although paragangliomas exhibit a wide variability of uptake. Low to moderate level 68 Ga-DOTATATE uptake is nonspecific and may represent diverse pathophysiology including paraganglioma, meningioma, and other neuroaxis tumors but essentially excludes schwannomas, which exhibited virtually no uptake.

Long-term quality of life after treatment in sinonasal malignancy: A prospective, multicenter study.

BACKGROUND: Quality of life (QOL) for individuals with sinonasal malignancy (SNM) is significantly under-studied, yet it is critical for counseling and may impact treatment. In this study we evaluated how patient, treatment, and disease factors impact sinonasal-specific and generalized QOL using validated metrics in a large cohort over a 5-year posttreatment time frame. METHODS: Patients with SNM who underwent definitive treatment with curative intent were enrolled in a prospective, multisite, longitudinal observational study. QOL was assessed using the 22-item Sino-Nasal Outcome Test (SNOT-22) and University of Washington Quality of Life Questionnaire (UWQOL) instruments at pretreatment baseline and multiple follow-ups through 5 years posttreatment. Multivariable modeling was used to determine demographic, disease, and treatment factors associated with disease-specific and generalized physical and social/emotional function QOL. RESULTS: One hundred ninety-four patients with SNM were analyzed. All QOL indices were impaired at pretreatment baseline and improved after treatment. SNOT-22 scores improved 3 months and UWQOL scores improved 6 to 9 months posttreatment. Patients who underwent open compared with endoscopic tumor resection had worse generalized QOL (p < 0.001), adjusted for factors including T stage. Pterygopalatine fossa (PPF) involvement was associated with worse QOL (SNOT-22, p < 0.001; UWQOL Physical dimension, p = 0.02). Adjuvant radiation was associated with worse disease-specific QOL (p = 0.03). Neck dissection was associated with worse generalized physical function QOL (p = 0.01). Positive margins were associated with worse generalized social/emotional function QOL (p = 0.01). CONCLUSION: Disease-specific and generalized QOL is impaired at baseline in patients with SNM and improves after treatment. Endoscopic resection is associated with better QOL. PPF involvement, adjuvant radiation, neck dissection, and positive margins were associated with worse QOL posttreatment.

The Influence of Radiologist Practice Setting on Identification of Vascular Compression from Magnetic Resonance Imaging in Trigeminal Neuralgia.

OBJECTIVE: Preoperative magnetic resonance imaging (MRI) studies are routinely ordered for trigeminal neuralgia (TN), though with contested reliability in contemporary literature. A potential reason for this disagreement is inconsistency in MRI reading methodologies. Here, we compare the rate of reported neurovascular compression on preoperative MRI by radiologists employed in community or private practice settings and academic neuroradiologists. METHODS: A retrospective review was conducted on patients who underwent endoscopic microvascular decompression for TN with intraoperatively visualized neurovascular compression and primary read by a non-academic or community radiologist. Patient imaging was then re-read by a board-certified neuroradiologist practicing in an academic setting, who was blinded to the initial read and the side of TN symptoms. RESULTS: Non-academic radiologists reported vascular compression in 26.0% (20/77) of all patients, and mention was rarely made of the non-pathological side (sensitivity = 26.0%). On academic neuroradiologist re-reads, vascular compression was noted in 87.0% (67/77) of patients on the pathological side and in 57.1% (44/77) on the non-pathological side (sensitivity = 87.0%, specificity = 42.9%). Isotropic/near isotropic 3-dimensional steady state or heavily T2-weighted sequences were read with 92.3% sensitivity and 36.9% specificity, compared to 58.3% sensitivity and 66.7% specificity using routine T2 weighted sequences. CONCLUSIONS: The frequency of vascular compression reported by non-academic radiologists is much lower than what is reported by academic neuroradiologists reading the same MRI scans. These results highlight the effect of practice setting on the predictive power of neuroimaging. Future studies are indicated to further investigate these relationships, as well as to trial newer imaging modalities.

Multi-institutional review of sinonasal and skull base chondrosarcoma: 20-year experience.

BACKGROUND: Chondrosarcomas of the sinonasal cavity and skull base are uncommon malignancies. We sought to provide long-term outcomes at two tertiary care centers. METHODS: Patients with chondrosarcoma treated between 2000 and 2021 were included. The primary outcomes were overall survival (OS) and disease-specific survival (DSS). RESULTS: Thirty-eight patients met inclusion criteria. Fourteen patients had sinonasal (36.8%), 7 petroclival (18.4%), and 17 other primary skull base lesions (44.7%). Twenty-eight patients (73.7%) underwent radiation with an average dose of 67.3 ± 15.1 Gy. Eighteen patients (47.4%) required revision surgery for recurrence. 1, 5, and 10-year OS were 97.3%, 93.1%, and 74.7%. DSS at 5- and 10-year survival was 95.7%. Adjuvant radiation was associated with improved OS (HR: 0.12; 95% CI: 0.02-0.75, p = 0.023). CONCLUSION: We present our experience over the last 20 years treating chondrosarcomas. Favorable survival outcomes can be achieved but recurrence requiring repeat resection is common.

Retropharyngeal Internal Carotid Artery Management in TORS Using Microvascular Reconstruction.

OBJECTIVES: Guidelines for transoral robotic surgery (TORS) have generally regarded patients with retropharyngeal carotid arteries as contraindicated for surgery due to a theoretical risk of intraoperative vascular injury and/or perioperative cerebrovascular accident. We aimed to demonstrate that careful TORS-assisted resection and free flap coverage could not only avoid intraoperative injury and provide a physical barrier for vessel coverage but also achieve adequate margin control. STUDY DESIGN: Retrospective cohort analysis. METHODS: Retrospective review of patients with oropharyngeal malignancies and radiologically confirmed retropharyngeal carotid arteries who underwent TORS, concurrent neck dissection, and free flap reconstruction between 2015 and 2019. RESULTS: Twenty patients were included, 19 (95.0%) with tonsillar tumors and one (5.0%) with a tongue base tumor with significant tonsillar extension. Eighteen patients (90.0%) received a radial artery forearm flap, one (5.0%) an ulnar artery forearm flap, and one (5.0%) an anteromedial thigh flap. All 20 (100%) flaps were inset through combined transcervical and transoral approaches without mandibulotomy. There were no perioperative mortalities, carotid injuries, oropharyngeal bleeds, cervical hematomas, or cerebrovascular accidents. One patient (5.0%) had a free flap failure requiring explant. All patients underwent decannulation and resumed a full oral diet. The mean length of hospitalization was 6.8 (standard deviation 1.2) days. One (5.0%) patient had a positive margin. CONCLUSION: In this analysis, 20 patients with oropharyngeal malignancy and retropharyngeal carotid arteries underwent TORS, neck dissection, and microvascular reconstruction without serious complication (perioperative mortality, vascular injury, or neurologic sequalae) with an acceptable negative margin rate. These results may lead to a reconsideration of a commonly held contraindication to TORS. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E821-E827, 2021.

68Ga-DOTATATE Uptake in an Endolymphatic Sac Tumor: Radiologic-Pathologic Correlation.

After dedicated CT and MRI, Ga-DOTATATE PET/CT was performed in a patient with a temporal bone mass with primary diagnostic considerations of an endolymphatic sac tumor versus a glomus jugulotympanicum paraganglioma. The Ga-DOTATATE PET showed mild radiotracer uptake in the mass (SUVmax, 10.9). After surgical resection, pathology revealed an endolymphatic sac tumor. Immunohistochemical staining demonstrated somatostatin receptor type 2A expression in the vasculature of the mass, but not in the tumor cells.

Epilepsy Lesion Localization is not Predicted by Developmental Venous Anomaly Location or its FDG-PET Metabolic Activity.

BACKGROUND AND PURPOSE: This study's purpose is to correlate location and metabolic activity of developmental venous anomalies (DVAs) in epilepsy patients to the seizure focus as determined by ictal/interictal encephaloelectrogram (EEG). METHODS: A retrospective search was performed for epilepsy patients with DVAs who underwent brain 18 F-fluorodeoxyglucose positron emission tomography (18 F-FDG-PET) and magnetic resonance imaging (MRI). MRI exams were analyzed to characterize DVA location and associated structural findings. MRI and PET images were co-registered and assessment of 18 F-FDG uptake in the DVA territory was performed. The electronic medical record was reviewed for each subject to determine seizure semiology and site of seizure focus by ictal/interictal EEG. RESULTS: Twenty-eight DVAs in 25 patients were included. Twelve DVAs demonstrated regional metabolic abnormality on 18 F-FDG-PET. There was no significant correlation between DVA site and seizure focus on EEG. DVA location was concordant with EEG seizure focus in three subjects, and all three demonstrated hypometabolism on 18 F-FDG-PET. This significance remains indeterminate, as one of these DVAs was associated with cavernoma, which could serve as the true seizure focus, and one of the patients underwent resection of the DVA without decrease in seizure frequency. Furthermore, there was no statistically significant relationship between DVA metabolic activity and DVA-EEG lobar or laterality concordance. CONCLUSIONS: In this sample, there is no significant correlation between location of DVA and seizure focus, and hypometabolism within the DVA territory is not predictive of EEG/DVA co-localization. As use of 18 F-FDG-PET for evaluation of epilepsy increases, knowledge of this poor correlation is important to avoid diagnostic confusion and potentially unnecessary surgery in epilepsy patients.

Variations of the CNS Venous System Mimicking Pathology: Spectrum of Imaging Findings.

Variations in the venous drainage of the central nervous system can have imaging and clinical findings that mimic pathology, presenting a challenge for neuroimagers and clinicians. Patients with these variants may undergo unnecessary testing, and patients with pathology may receive delayed diagnoses because of overlap with benign findings. Consequently, the accurate identification of venous variations on cross-sectional imaging and angiography and their potential causes are critical for differentiating benign imaging variants from potential pathologic processes requiring further evaluation. For example, in the epidural space, benign dilation of the epidural venous plexus may be mistaken for evidence of a fistula, abscess, or metastasis. Hypoplasia of a dural venous sinus or an arachnoid granulation may mimic venous sinus thrombosis. The superior ophthalmic vein may demonstrate benign dilation in intubated patients, mimicking thrombosis, increased intracranial pressure, orbital varix, inflammatory pseudotumor, or other conditions. Furthermore, certain venous variations, such as the occipital sinus or emissary veins, may complicate surgery or herald pathology and should be reported. In addition, some supposedly benign variations, such as the developmental venous anomaly, can be complicated by pathology. The objective of this review article is to provide a descriptive and pictorial review of common anatomic and physiologic variations in the venous drainage system of the brain, spine, and orbits that can mimic pathology. Neuroimaging findings of related pathologies and differences in clinical presentations will also be discussed to assist in the approach to differential diagnosis.

Metabolic Changes of Brain Developmental Venous Anomalies on 18F-FDG-PET.

RATIONALE AND OBJECTIVES: To determine the metabolic effects of developmental venous anomalies (DVAs) and to correlate those effects with conventional magnetic resonance imaging (MRI) findings. MATERIALS AND METHODS: We conducted a retrospective review of MRI and brain 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) examinations in subjects with DVAs. Conventional MRI was used to determine DVA number, location, size, and associated parenchymal findings such as atrophy, hemorrhage, cavernoma, capillary telangiectasia, cortical dysplasia/polymicrogyria, and white matter signal abnormality. Qualitative and quantitative measures of relative metabolism in the drainage territory of the DVA were measured on 18F-FDG-PET. RESULTS: Fifty-four subjects with 57 DVAs were included in the analysis. 38% were associated with qualitative and quantitative metabolic abnormalities on 18F-FDG-PET, with decreased metabolism in the parenchyma surrounding all but one of these DVAs. DVAs draining gray matter were significantly more likely to be hypometabolic than those draining only white matter, suggesting that the metabolic effects of DVAs may be underestimated on 18F-FDG-PET. CONCLUSION: Altered metabolism is seen in the drainage territory of a significant proportion of DVAs, suggesting that these anomalies are vascular lesions with abnormal physiologic features.

An Imager's Guide to Perineural Tumor Spread in Head and Neck Cancers: Radiologic Footprints on 18F-FDG PET, with CT and MRI Correlates.

Perineural spread (PNS) refers to tumor growth along large nerves, a macroscopic analog of microscopic perineural invasion. This phenomenon most commonly occurs in the head and neck, but its incidence varies with histologic tumor subtype. PNS results from a complex molecular interplay between tumor cells, nerves, and connective stroma. PNS is clinically underdiagnosed despite its impact on patients' prognosis and management. The role of 18F-FDG PET in assessment of PNS in head and neck cancer remains to be explored, in contrast to MRI as the established gold standard. In patients with PNS, 18F-FDG PET shows both abnormality along the course of the involved nerve and muscular changes secondary to denervation. Assessment of PNS on 18F-FDG PET requires knowledge of relevant neural pathways and can be improved by correlation with anatomic imaging, additional processing of images, and review of clinical context.

Inhibition of STAT3 Tyr705 phosphorylation by Smad4 suppresses transforming growth factor beta-mediated invasion and metastasis in pancreatic cancer cells.

The role of Smad4 in transforming growth factor beta (TGFbeta)-mediated epithelial-mesenchymal transition (EMT), invasion, and metastasis was investigated using isogenically matched pancreatic cancer cell lines that differed only in expression of Smad4. Cells expressing Smad4 showed an enhanced TGFbeta-mediated EMT as determined by increased expression of vimentin and decreased expression of beta-catenin and E-cadherin. TGFbeta-mediated invasion was suppressed in Smad4-intact cells as determined by in vitro assays, and these cells showed a reduced metastasis in an orthotopic model of pancreatic cancer. Interestingly, TGFbeta inhibited STAT3(Tyr705) phosphorylation in Smad4-intact cells. The decrease in STAT3(Tyr705) phosphorylation was linked to a TGFbeta/Smad4-dependent and enhanced activation of extracellular signal-regulated kinases, which caused an increase in serine phosphorylation of STAT3(Ser727). Down-regulating signal transducer and activator of transcription 3 (STAT3) expression by short hairpin RNA in Smad4-deficient cells prevented TGFbeta-induced invasion. Conversely, expressing a constitutively activated form of STAT3 (STAT3-C) in Smad4-intact cells enhanced invasion. This study indicates the requirement of STAT3 activity for TGFbeta-induced invasion in pancreatic cancer cells and implicates Smad4-dependent signaling in regulating STAT3 activity. These findings further suggest that loss of Smad4, leading to aberrant activation of STAT3, contributes to the switch of TGFbeta from a tumor-suppressive to a tumor-promoting pathway in pancreatic cancer.