Determinants of Symptomatic Intracranial Progression After an Initial Stereotactic Radiosurgery Course.

Purpose: Clinical and imaging surveillance of patients with brain metastases is important after stereotactic radiosurgery (SRS) because many will experience intracranial progression (ITCP) requiring multidisciplinary management. The prognostic significance of neurologic symptoms at the time of ITCP is poorly understood. Methods and Materials: This was a multi-institutional, retrospective cohort study from 2015 to 2020, including all patients with brain metastases completing an initial course of SRS. The primary outcome was overall survival (OS) by presence of neurologic symptoms at ITCP. OS, freedom from ITCP (FF-ITCP), and freedom from symptomatic ITCP (FF-SITCP) were assessed via Kaplan-Meier method. Cox proportional hazard models tested parameters impacting FF-ITCP and FF-SITCP. Results: Among 1383 patients, median age was 63.4 years, 55% were female, and common primaries were non-small cell lung (49%), breast (15%), and melanoma (9%). At a median follow-up of 8.72 months, asymptomatic and symptomatic ITCP were observed in 504 (36%) and 194 (14%) patients, respectively. The majority of ITCP were distant ITCP (79.5%). OS was worse with SITCP (median, 10.2 vs 17.9 months, P < .001). SITCP was associated with clinical factors including total treatment volume (P = .012), melanoma histology (P = .001), prior whole brain radiation therapy (P = .003), number of brain metastases (P < .001), interval of 1 to 2 years from primary and brain metastasis diagnosis (P = .012), controlled extracranial disease (P = .042), and receipt of pre-SRS chemotherapy (P = .015). Patients who were younger and received post-SRS chemotherapy (P = .001), immunotherapy (P < .001), and targeted or small-molecule inhibitor therapy (P < .026) had better FF-SITCP. Conclusions: In this cohort study of patients with brain metastases completing SRS, neurologic symptoms at ITCP is prognostic for OS. This data informs post-SRS surveillance in clinical practice as well as future prospective studies needed in the modern management of brain metastases.

Demystifying radiation oncology clinical trial concerns for protocol scientific review and institutional review board committee members.

Clinical trials are essential for evaluating advanced technologies and treatment approaches involving radiation therapy to improve outcomes for cancer patients. Clinical trials at cancer centers with designation from the National Cancer Institute must undergo scientific review in additional to Institutional Review Board approval. Given the highly specialized nature and rapidly advancing technologies of radiation therapy, and the small number of radiation oncology investigators at some centers, a lack of radiation oncology expertise among reviewers may present challenges at some cancer centers. This commentary aims to provide an overview of radiation therapy and special considerations for radiation oncology research that will serve as a helpful resource in the scientific review of clinical trials involving cancer patients.

Patterns of distant metastases in 215 Merkel cell carcinoma patients: Implications for prognosis and surveillance.

Approximately one-third of Merkel cell carcinoma (MCC) patients eventually develop distant metastatic disease. Little is known about whether the location of the primary lesion is predictive of initial distant metastatic site, or if survival likelihood differs depending on the metastatic site. Such data could inform imaging/surveillance practices and improve prognostic accuracy. Multivariate and competing-risk analyses were performed on a cohort of 215 MCC patients with distant metastases, 31% of whom had two or more initial sites of distant metastasis. At time of initial distant metastasis in the 215 patients, metastatic sites (n = 305) included non-regional lymph nodes (present in 41% of patients), skin/body wall (25%), liver (23%), bone (21%), pancreas (8%), lung (7%), and brain (5%). Among the 194 patients who presented with MCC limited to local or regional sites (stage I-III) but who ultimately developed distant metastases, distant progression occurred in 49% by 1 year and in 80% by 2 years following initial diagnosis. Primary MCC locations differed in how likely they were to metastasize to specific organs/sites (P < .001). For example, liver metastases were far more likely from a head/neck primary (43% of 58 patients) versus a lower limb primary (5% of 39 patients; P < .0001). Skin-only distant metastasis was associated with lower MCC-specific mortality as compared to metastases in multiple organs/sites (HR 2.7; P = .003), in the liver (HR 2.1; P = .05), or in distant lymph nodes (HR 2.0; P = .045). These data reflect outcomes before PD1-pathway inhibitor availability, which may positively impact survival. In conclusion, primary MCC location is associated with a pattern of distant spread, which may assist in optimizing surveillance. Because it is linked to survival, the site of initial distant metastasis should be considered when assessing prognosis.

Statin use protective for chronic rhinosinusitis in a nationally representative sample of the United States.

OBJECTIVES/HYPOTHESIS: Statins have long been used in the management of cardiovascular disease for their lipid-lowering properties. However, recent research suggests that statins may also have anti-inflammatory effects via modulation of lipid-containing enzymes and mediators, and therefore may have therapeutic value in the treatment of chronic rhinosinusitis (CRS). STUDY DESIGN: Retrospective database review. METHODS: The 2006 to 2015 National Ambulatory Medical Care Survey (NAMCS) data were queried to analyze the relationship between statin use and rates of CRS. CRS was indicated by the presence of an International Classification of Diseases, Ninth Revision code for CRS in one of the five diagnosis variables. Statin use was indicated by the presence of a statin medication in any of the 30 medication variables using the Multum Lexicon Drug Database, with newly prescribed medications excluded. Relevant demographic, socioeconomic, and comorbid factors were included in a multivariate logistic regression model, which accounted for the complex, stratified, multistage survey design of the NAMCS. RESULTS: There were 390,538 unweighted visit records used in the weighted analysis dataset, corresponding to 9,612,613,668 weighted visits. Statin use was associated with a decreased rate of CRS in both a univariate analysis (odds ratio [OR] = 0.53, P < .001) and the multivariate logistic regression accounting for comorbid, socioeconomic, and demographic factors (OR = 0.79, P = .030). CONCLUSIONS: Statin use is associated with decreased rates of CRS based on a nationally representative sample of outpatient visits in the United States. This supports research that suggests statin medications may have protective properties against CRS, and further research is warranted into their potential therapeutic value for this indication. LEVEL OF EVIDENCE: NA Laryngoscope, 130:848-851, 2020.

Association Between Olfactory and Gustatory Dysfunction and Cognition in Older Adults.

BACKGROUND: The association between olfactory dysfunction (OD) and cognitive decline is becoming apparent in the emerging literature. However, the literature demonstrating a similar effect between gustatory dysfunction (GD) and cognition is not well established. OBJECTIVE: To determine whether OD and GD are independently associated with cognitive impairment. METHODS: The 2013-2014 National Health and Nutrition Examination Survey was queried for 1376 older adults, corresponding to a weighted population sample of 50 816 529, to assess olfactory and gustatory status and cognition using univariate and multivariate regression analyses. OD and GD were determined using objective measurements with validated protocols. Participants were stratified as normal or abnormal cognition status using accepted cutoff values as indicated for the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological test, Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). RESULTS: OD was associated with both mild cognitive impairment (odds ratio [OR] 1.809, P = .004) and dementia (OR 3.173, P < .001) with CERAD testing, abnormal AFT (OR 2.424, P < .001), and abnormal DSST (OR 4.028, P < .001). GD based on 1M NaCl whole mouth taste testing was associated with dementia on CERAD testing (OR 2.217, P = .004). When smell and taste parameters were included together in the regression model, both OD and GD remained significant independent predictors of dementia status based on CERAD testing (OR 3.133, P < .001, OR 1.904, P = .015). CONCLUSIONS: OD and severe GD represent independent predictors of cognitive impairment in a nationally representative sample of older adults.