A Report on the Safety of Acitretin Use in Renal Failure Patients on Hemodialysis.

Acitretin, commonly used for severe psoriasis and keratinocyte carcinoma chemoprevention in high-risk patients, is contraindicated in patients with end stage renal disease on hemodialysis. However, these patients often lack medication choices and in certain clinical scenarios, the benefits of acitretin may outweigh the potential risks. We identified 24 end stage renal disease patients on HD taking acitretin from Duke and Vanderbilt University Medical Centers. While adverse effects were common, patients did not frequently discontinue the medication due to them. We also found no association between acitretin with hospital admissions or mortality. We lastly found statistically significant increases in ALP and total bilirubin when on acitretin and dialysis compared to baseline. However, there was no dose-dependency or temporal association with acitretin or hemodialysis initiation. Based off these preliminary findings, we find that acitretin may safely be used in patients receiving HD with close monitoring of ALP and bilirubin.

The impact of salvage radiotherapy initiation at PSA ≤ 0.5 ng/ml on metastasis-free survival in patients with relapsed prostate cancer following prostatectomy.

BACKGROUND AND PURPOSE: Salvage radiation therapy (SRT) is indicated for biochemical failure after radical prostatectomy. Prior data have shown that initiation of SRT at lower PSA levels improves subsequent biochemical control, yet given the long natural history of prostate cancer questions remain regarding optimal timing of SRT. We analyzed the impact of prostate specific antigen (PSA) level at time of salvage radiotherapy with regard to both biochemical relapse-free (bRFS) as well as metastasis-free survival (MFS) in patients with biochemically recurrent prostate cancer. METHODS: Using prospective institutional tumor registry data, univariate and multivariable-adjusted Cox proportional hazards models were constructed to assess association between outcomes and clinical and pathologic prognostic features, including pre-SRT PSA, interval from prostatectomy to SRT, androgen deprivation therapy (ADT), and adverse pathologic features. RESULTS: We identified 397 patients who received salvage RT between 1985 and 2016: 187 (45.8%) received SRT initiated when pre-RT PSA was ≤0.5 ng/ml; 212 (52.0%) patients had pre-SRT PSA > 0.5 ng/ml. Independent of pathologic risk status and ADT use, pre-SRT PSA ≤ 0.5 ng/ml was the most significant predictor of bRFS (HR 0.39, 95% CI [0.27, 0.56]) as well as MFS (HR = 0.58, 95% CI [0.37, 0.91]). Seminal vesicle invasion was also associated with shorter interval to biochemical failure, HR = 1.79, 95% CI [1.07, 2.98], and eventual metastases, HR = 2.07, 95% CI [1.14, 3.740]. CONCLUSIONS: Initiation of salvage RT while PSA levels remain ≤0.5 ng/ml was associated with improved MFS. Consideration for salvage RT initiation while PSA levels remain low is warranted to minimize risk of future prostate cancer metastasis.

A multi-site phase I trial of Veliparib with standard radiation and temozolomide in patients with newly diagnosed glioblastoma multiforme (GBM).

PURPOSE: A multi-site Phase I trial was conducted to determine the safety, maximum tolerated dose, and pharmacokinetics (PK) of Veliparib, a Poly (ADP-ribose) polymerase [PARP] enzyme inhibitor, when administered with temozolomide (TMZ) alone and then with temozolomide and radiation (RT) in patients with newly diagnosed glioblastoma. METHODS: Given the potential for myelosuppression when a PARP inhibitor is combined with chemotherapy, the first 6 patients accrued were given Veliparib 10 mg bid and TMZ 75 mg/m2/d daily for six weeks. If this was well tolerated, the same doses of Veliparib and TMZ would be tested along with standard radiation with plans to dose escalate the Veliparib in subsequent patient cohorts. Once a maximal tolerated dose was determined, a 78 patient phase II study was planned. Peripheral blood pharmacokinetics were assessed. RESULTS: Twenty-four patients were enrolled. In the first 6 patients who received 6 weeks of TMZ with Veliparib only one dose limiting toxicity (DLT) occurred. The next 12 patients received 6 weeks of RT + TMZ + veliparib and 4/12 (33%) had dose limiting hematologic toxicities. As a result, Veliparib was reduced by 50% to 10 mg BID every other week, but again 3/3 patients had dose limiting hematologic toxicities. The trial was then terminated. The mean clearance (± SD) CL/F of Veliparib for the initial dose (27.0 ± 9.0 L/h, n = 16) and at steady-state for 10 mg BID (23.5 ± 10.4 L/h, n = 18) were similar. Accumulation for BID dosing was 56% (± 33%). CONCLUSIONS: Although Veliparib 10 mg BID administered with TMZ 75 mg/m2 for six weeks was well tolerated, when this regimen was combined with standard partial brain irradiation it was severely myelosuppressive even when the dose was reduced by 50%. This study again highlights the potential of localized cranial radiotherapy to significantly increase hematologic toxicity of marginally myelosuppressive systemic therapies.

The Rhytidectomy Scar: Analysis of Patient and Surgeon Perspectives.

An understanding of patient preference is vital for surgeons to create outcomes that align with the goals of patients undergoing cosmetic surgery. This study analyzes the perception of the rhytidectomy scar from the perspective of cosmetic patients and surgeons. Cross-sectional surveys were administered in-person to cosmetic patients and online to facial plastic and reconstructive surgeons in the United States. Participants were presented with standardized lateral view photographs of preauricular scars for 10 patients at least 12 months post rhytidectomy procedure. A variety of rhytidectomy incisions were chosen to include pre- versus post-tragal incisions, blunted hair tuft, hypopigmentation, narrow versus wide scar healing. Participants were asked to rate the outcome of the preauricular rhytidectomy scar using the Likert scale from 1 to 10. Quantitative analysis indicates that while both surgeons and cosmetic patients viewed hypopigmented scars less favorably, surgeons were more concerned with pre-tragal incision and blunted hair tuft. Furthermore, the number of rhytidectomies performed by surgeons resulted in more critical analysis of the scars presented in this study. Qualitative analysis of the frequent use of "natural" in the patient comments suggests the importance of maintaining a sense of "normalcy" as well. In contrast, the surgeon comments are most frequently about the relationship between the scar and surrounding anatomical structures, suggesting a descriptive focus on the technicality of scar placement and subsequent anatomical result. Cosmetic patients are primarily concerned about scar appearance while surgeons are more focused on the technical orientation of the scar. An understanding and comparison of the language and perceptions of surgeons and cosmetic patients regarding rhytidectomy scars are vital in creating aesthetic results and managing patient expectations.

Comparison of Outcomes for One-View Asymmetries Recalled From Digital Breast Tomosynthesis Versus Full-Field Digital Mammography Screening Examinations.

BACKGROUND. Recall rates are lower for digital breast tomosynthesis (DBT) than for full-field digital mammography (FFDM). This difference could have important implications with respect to one-view asymmetries given that missed cancers are often visible on one view. OBJECTIVE. The purpose of this study is to compare the outcomes of one-view asymmetries recalled from DBT versus FFDM screening examinations and to determine predictors of malignancy among recalled asymmetries. METHODS. This retrospective study first determined recall rates associated with one-view asymmetries for screening mammography performed using DBT and FFDM from July 14, 2016, through July 14, 2020. Further analyses included patients recalled for a one-view asymmetry who completed subsequent diagnostic workup and all recommended follow-up. Patient and cancer characteristics were extracted from the electronic health record. RESULTS. The recall rate associated with asymmetries was lower for DBT screening (2.5% [3169/128,755]) than for FFDM screening (3.4% [815/23,898]) (p < .001). Further analyses of patients who completed diagnostic workup and subsequent follow-up included 3119 patients (mean age, 57 years) for DBT screening and 811 patients (mean age, 56 years) for FFDM screening. Distribution of final BI-RADS categories from subsequent diagnostic workup was not different between the two modalities (p > .99). The frequency of malignancy was not different between asymmetries recalled from DBT (1.7% [54/3119]) and FFDM (1.7% [14/811]) (p > .99). Malignant asymmetries identified on FFDM versus DBT were more frequently associated with architectural distortion on diagnostic workup (35.7% [5/14] vs 9.3% [5/54]) (p < .001) and were more commonly invasive ductal carcinoma (92.9% vs 57.4%) and less commonly invasive lobular carcinoma (0.0% vs 24.1%) (p = .05). In multivariable analysis, independent predictors of malignancy among recalled asymmetries from DBT were age (for 55-69 years, odds ratio [OR] = 2.40 [p = .04]; for ≥ 70 years, OR = 7.93 [p < .001]; reference, < 55 years) and breast density (not dense, OR = 2.47 [p = .001]; reference, dense breasts). CONCLUSION. Recalled asymmetries were less frequent for DBT than for FFDM. The malignancy rate was low for both modalities (1.7%). Age 55 years old and older and lower breast density predicted malignancy for DBT-recalled asymmetries. CLINICAL IMPACT. Our results support the use of DBT to reduce unnecessary recalls without altering PPV for asymmetry-associated malignancies. Patient factors should be considered when assessing whether a potential asymmetry on DBT screening represents overlapping fibroglandular tissue or a suspicious finding that requires diagnostic workup.

Vascular findings in CTA body and extremity of critically ill COVID-19 patients: commonly encountered vascular complications with review of literature.

The purpose of our review is to discuss the role of CT angiography (CTA) in evaluating a variety of vascular complications in critically ill COVID-19 patients. The COVID-19 pandemic continues to be a worldwide health threat. While COVID-19 pneumonia is the most common and well-recognized presentation of COVID-19, severely ill hospitalized patients often present with extrapulmonary systemic findings. Vascular complications occur not only due to known viral-induced vasculopathy, coagulopathy, and related "cytokine storm," but also due to anticoagulation medication used during hospitalization. There is a paucity of articles describing extrapulmonary vascular findings, especially in critically ill COVID-19 patients. In our article, we discuss commonly encountered vascular imaging findings in the body (chest, abdomen, and pelvis) and extremities, the importance of early radiological detection, and the role of CTA in the management of critically ill COVID-19 patients.

Attachment of flagellin enhances the immunostimulatory activity of a hemagglutinin-ferritin nano-cage.

Hemagglutinin (HA) displayed on a ferritin nano-cage has been shown to be effective in generating a potent immune response against a broad range of influenza infections. Here, we showed that conjugation of flagellin together with HA to the exterior surface of the ferritin cage greatly enhanced not only the humoral immune response in mice but also antigen-specific T cell responses that include Th1 cytokine secretion. The effect of flagellin remained essentially unchanged when the molar ratio of flagellin to HA was reduced from 1:1 to 1:3. Injection of the ferritin-HA-flagellin cage provided protection against lethal virus challenge in mice. We used a small immunoglobulin fragment VL12.3 as a convenient method for attaching HA and flagellin to the ferritin cage. This attachment method can be used for rapid screening of a variety of protein cages and nano-assemblies to identify the most suitable carrier and adjuvant proteins for the target antigen.

PTEN Loss Is Associated with Adverse Outcomes in the Setting of Salvage Radiation Therapy.

BACKGROUND: Salvage radiation therapy (SRT) is a mainstay of treatment for biochemical relapse following radical prostatectomy; however, few studies have examined genomic biomarkers in this context. OBJECTIVE: We characterized the prognostic impact of previously identified deleterious molecular phenotypes-loss of PTEN, ERG expression, and TP53 mutation-for patients undergoing SRT. DESIGN, SETTING, AND PARTICIPANTS: We leveraged an institutional database of 320 SRT patients with available tissue and follow-up. Tissue microarrays were used for genetically validated immunohistochemistry assays. INTERVENTION: All men underwent SRT with or without androgen deprivation therapy OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable and multivariable Cox-proportional hazard models assessed the association of molecular phenotypes with biochemical recurrence-free (bRFS) and metastasis-free (MFS) survival after SRT. RESULTS AND LIMITATIONS: Loss of PTEN (n = 123, 43%) and ERG expression (n = 118, 39%) were common in this cohort, while p53 overexpression (signifying TP53 missense mutation) was infrequent (n = 21, 7%). In univariable analyses, any loss of PTEN portended worse bRFS (hazard ratio [HR] 1.86; 95% confidence interval 1.36-2.57) and MFS (HR 1.89; 1.21-2.94), with homogeneous PTEN loss being associated with the highest risk of MFS (HR 2.47; 1.54-3.95). Similarly, p53 overexpression predicted worse bRFS (HR 1.95; 1.14-3.32) and MFS (HR 2.79; 1.50-5.19). ERG expression was associated with worse MFS only (HR 1.6; 1.03-2.48). On the multivariable analysis adjusting for known prognostic features, homogeneous PTEN loss remained predictive of adverse bRFS (HR 1.82; 1.12-2.96) and MFS (HR 2.08; 1.06-4.86). The study is limited by its retrospective and single-institution design. CONCLUSIONS: PTEN loss by immunohistochemistry is an independent adverse prognostic factor for bRFS and MFS in prostate cancer patients treated with SRT. Future trials will determine the optimal approach to treating SRT patients with adverse molecular prognostic features. PATIENT SUMMARY: Loss of the PTEN tumor suppressor protein is associated with worse outcomes after salvage radiotherapy, independent of other clinical or pathologic patient characteristics.

Impact of Patient Navigation on Reducing Breast Imaging Disparities and Applications in the COVID-19 Era.

The coronavirus (COVID-19) pandemic has impacted breast cancer screening with concerns that this may lead to increased overall breast cancer mortality and worsened racial and ethnic disparities in breast cancer survival. As pandemic recovery efforts are underway, we must be prepared to address barriers to timely access of breast imaging services, including those that existed prior to the pandemic, as well as any new barriers that may arise as a result of the pandemic. Patient navigation is an important tool that has been shown to address barriers to timely breast imaging access and help reduce disparities. Patient navigation programs can serve as a key part of the strategy to mitigate the impact of the COVID-19 pandemic on timely breast cancer diagnosis. These programs have been shown to be successful in promoting adherence to breast cancer screening guidelines as well as encouraging timely diagnostic follow-up, particularly in underserved communities. Further research is needed to explore the role of using a telehealth platform for patient navigation and evaluate the cost-effectiveness of patient navigator programs as well as more randomized controlled trials to further explore the impact of patient navigation programs.

Interval Breast Cancers Versus Screen Detected Breast Cancers: A Retrospective Cohort Study.

RATIONALE AND OBJECTIVE: Mammographic screening detects most breast cancers but there are still women diagnosed with breast cancer between annual mammograms. We aim to identify features that differentiate screen detected breast cancers from interval breast cancer. MATERIALS AND METHODS: All screening mammograms (n = 211,517) performed 7/1/2013-6/30/2020 at our institution were reviewed. Patients with breast cancer diagnosed within one year of screening were included and divided into two distinct groups: screen detected cancer group and interval cancer group. Characteristics in these groups were compared using the chi square test, fisher test, and student's T test. RESULTS: A total of 1,232 patients were included (mean age 64 +/- 11). Sensitivity of screening mammography was 92% (1,136 screen detected cancers, 96 interval cancers). Patient age, race, and personal history of breast cancer were similar between the groups (p > 0.05). Patients with interval cancers more often had dense breast tissue (75/96 = 78% versus 694/1136 = 61%, p < 0.001). Compared to screen detected cancers, interval cancers were more often primary tumor stage two or higher (41/96 = 43% versus 139/1136 = 12%, p < 0.001) and regional lymph node stage one or higher (21/96 = 22% versus 132/1136 = 12%, p = 0.003). Interval cancers were more often triple negative (16/77 = 21% versus [48/813 = 6%], p < 0.001) with high Ki67 proliferation indices (28/45 = 62% versus 188/492 = 38%, p = 0.002). CONCLUSION: Mammographic screening had high sensitivity for breast cancer detection (92%). Interval cancers were associated with dense breast tissue and had higher stage with less favorable molecular features compared to screen detected cancers.

A Multidimensional Connectomics- and Radiomics-Based Advanced Machine-Learning Framework to Distinguish Radiation Necrosis from True Progression in Brain Metastases.

We introduce tumor connectomics, a novel MRI-based complex graph theory framework that describes the intricate network of relationships within the tumor and surrounding tissue, and combine this with multiparametric radiomics (mpRad) in a machine-learning approach to distinguish radiation necrosis (RN) from true progression (TP). Pathologically confirmed cases of RN vs. TP in brain metastases treated with SRS were included from a single institution. The region of interest was manually segmented as the single largest diameter of the T1 post-contrast (T1C) lesion plus the corresponding area of T2 FLAIR hyperintensity. There were 40 mpRad features and 6 connectomics features extracted, as well as 5 clinical and treatment factors. We developed an Integrated Radiomics Informatics System (IRIS) based on an Isomap support vector machine (IsoSVM) model to distinguish TP from RN using leave-one-out cross-validation. Class imbalance was resolved with differential misclassification weighting during model training using the IRIS. In total, 135 lesions in 110 patients were analyzed, including 43 cases (31.9%) of pathologically proven RN and 92 cases (68.1%) of TP. The top-performing connectomics features were three centrality measures of degree, betweenness, and eigenvector centralities. Combining these with the 10 top-performing mpRad features, an optimized IsoSVM model was able to produce a sensitivity of 0.87, specificity of 0.84, AUC-ROC of 0.89 (95% CI: 0.82-0.94), and AUC-PR of 0.94 (95% CI: 0.87-0.97).

Developing the POTOMAC Model: A Novel Prediction Model to Study the Impact of Lymphopenia Kinetics on Survival Outcomes in Head and Neck Cancer Via an Ensemble Tree-Based Machine Learning Approach.

PURPOSE: Lymphopenia is associated with poor survival outcomes in head and neck squamous cell carcinoma (HNSCC), yet there is no consensus on whether we should limit lymphopenia risks during treatment. To fully elucidate the prognostic role of baseline versus treatment-related lymphopenia, a robust analysis is necessary to investigate the relative importance of various lymphopenia metrics (LMs) in predicting survival outcomes. METHODS: In this prospective cohort study, 363 patients were eligible for analysis (patients with newly diagnosed, nonmetastatic HNSCC treated with neck radiation with or without chemotherapy in 2015-2019). Data were acquired on 28 covariates: seven baseline, five disease, seven treatment, and nine LMs, including static and time-varying features for absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio, and immature granulocytes (IGs). IGs were included, given their hypothesized role in inhibiting lymphocyte function. Overall, there were 4.0% missing data. Median follow-up was 2.9 years. We developed a model (POTOMAC) to predict survival outcomes using a random survival forest (RSF) procedure. RSF uses an ensemble approach to reduce the risk of overfitting and provides internal validation of the model using data that are not used in model development. The ability to predict survival risk was assessed using the AUC for the predicted risk score. RESULTS: POTOMAC predicted 2-year survival with AUCs at 0.78 for overall survival (primary end point) and 0.73 for progression-free survival (secondary end point). Top modifiable risk factors included radiation dose and max ALC decrease. Top baseline risk factors included age, Charlson Comorbidity Index, Karnofsky Performance Score, and baseline IGs. Top-ranking LMs had superior prognostic performance when compared with human papillomavirus status, chemotherapy type, and dose (up to 2, 8, and 65 times higher in variable importance score). CONCLUSION: POTOMAC provides important insights into potential approaches to reduce mortality in patients with HNSCC treated by chemoradiation but needs to be validated in future studies.

A Multi-Site Phase I Trial of Veliparib with Standard Radiation and Temozolomide in Patients with Newly Diagnosed Glioblastoma Multiforme (GBM).

Purpose: A multi-site Phase I trial was conducted to determine the safety, maximum tolerated dose, and pharmacokinetics (PK) of Veliparib, a Poly (ADP-ribose) polymerase [PARP] enzyme inhibitor, when administered with temozolomide (TMZ) alone and then with temozolomide and radiation (RT) in patients with newly diagnosed glioblastoma. Methods: Given the potential for myelosuppression when a PARP inhibitor is combined with chemotherapy, the first 6 patients accrued were given Veliparib 10 mg bid and TMZ 75 mg/m2/d daily for six weeks. If this was well tolerated, the same doses of Veliparib and TMZ would be tested along with standard radiation with plans to dose escalate the Veliparib in subsequent patient cohorts. Once a maximal tolerated dose was determined, a 78 patient phase II study was planned. Peripheral blood pharmacokinetics were assessed. Results: Twenty-four patients were enrolled. In the first 6 patients who received 6 weeks of TMZ with Veliparib only one dose limiting toxicity (DLT) occurred. The next 12 patients received 6 weeks of RT + TMZ + veliparib and 4/12 (33%) had dose limiting hematologic toxicities. As a result, Veliparib was reduced by 50% to 10 mg BID every other week, but again 3/3 patients had dose limiting hematologic toxicities. The trial was then terminated. The mean clearance (± SD) CL/F of Veliparib for the initial dose (27.0 ± 9.0 L/h, n = 16) and at steady-state for 10 mg BID (23.5 ± 10.4 L/h, n = 18) were similar. Accumulation for BID dosing was 56% (± 33%). Conclusions: Although Veliparib 10 mg BID administered with TMZ 75 mg/m2 for six weeks was well tolerated, when this regimen was combined with standard partial brain irradiation it was severely myelosuppressive even when the dose was reduced by 50%. This study again highlights the potential of localized cranial radiotherapy to significantly increase hematologic toxicity of marginally myelosuppressive systemic therapies.

Induction of double-strand breaks with the non-steroidal androgen receptor ligand flutamide in patients on androgen suppression: a study protocol for a randomized, double-blind prospective trial.

BACKGROUND: Prostate cancer remains the most prevalent malignancy and the second-leading cause of cancer-related death in men in the USA. Radiation therapy, typically with androgen suppression, remains a mainstay in the treatment of intermediate- and high-risk, potentially lethal prostate cancers. However, local recurrence and treatment failure remain common. Basic and translational research has determined the potential for using androgen receptor (AR) ligands (e.g., dihydrotestosterone and flutamide) in the context of androgen-deprived prostate cancer to induce AR- and TOP2B-mediated DNA double-strand breaks (DSBs) and thereby synergistically enhance the effect of radiation therapy (RT). The primary aim of this study is to carry out pharmacodynamic translation of these findings to humans. METHODS: Patients with newly diagnosed, biopsy-confirmed localized prostatic adenocarcinoma will be recruited. Flutamide, an oral non-steroidal androgen receptor ligand, will be administered orally 6-12 h prior to prostate biopsy (performed under anesthesia prior to brachytherapy seed implantation). Key study parameters will include the assessment of DNA double-strand breaks by γH2A.x foci and AR localization to the nucleus. The initial 6 patients will be treated in a single-arm run-in phase to assess futility by establishing whether at least 2 subjects from this group develop γH2A.x foci in prostate cancer cells. If this criterion is met, the study will advance to a two-arm, randomized controlled phase in which 24 participants will be randomized 2:1 to either flutamide intervention or placebo standard-of-care (with all patients receiving definitive brachytherapy). The key pharmacodynamic endpoint will be to assess whether the extent of γH2A.x foci (proportion of cancer cells positive and number of foci per cancer cell) is greater in patients receiving flutamide versus placebo. Secondary outcomes of this study include an optional, exploratory analysis that will (a) describe cancer-specific methylation patterns of cell-free DNA in plasma and urine and (b) assess the utility of serum and urine samples as a DNA-based biomarker for tracking therapeutic response. DISCUSSION: This study will confirm in humans the pharmacodynamic effect of AR ligands to induce transient double-strand breaks when administered in the context of androgen deprivation as a novel therapy for prostate cancer. The findings of this study will permit the development of a larger trial evaluating flutamide pulsed-dose sequencing in association with fractionated external beam RT (+/- brachytherapy). The study is ongoing, and preliminary data collection and recruitment are underway; analysis has yet to be performed. TRIAL REGISTRATION: ClinicalTrials.gov NCT03507608. Prospectively registered on 25 April 2018.

Safety and clinical efficacy of immune checkpoint inhibition and stereotactic body radiotherapy in patients with spine metastasis.

OBJECTIVE: Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has revolutionized the treatment of patients with many tumor histologies. Simultaneously, stereotactic body radiotherapy (SBRT) provides excellent local control (LC) and plays an important role in the management of spine metastasis. Promising preclinical work suggests the potential therapeutic benefit of combining SBRT with ICI therapy, but the safety profile of combined therapy is unclear. This study aimed to evaluate the toxicity profile associated with ICI in patients receiving SBRT and, secondarily, whether ICI administration sequence with respect to SBRT affects LC or overall survival (OS) outcomes. METHODS: The authors retrospectively reviewed patients with spine metastasis treated with SBRT at an academic center. Patients who received ICI at any point during their disease course were compared to those with the same primary tumor types who did not receive ICI by using Cox proportional hazards analyses. Primary outcomes were long-term sequelae, including radiation-induced spinal cord myelopathy, esophageal stricture, and bowel obstruction. Secondarily, models were created to evaluate OS and LC in the cohort. RESULTS: Two hundred forty patients who received SBRT to 299 spine metastases were included in this study. The most common primary tumor types were non-small cell lung cancer (n = 59 [24.6%]) and renal cell carcinoma (n = 55 [22.9%]). One hundred eight patients received at least 1 dose of ICI, with the most common regimen being single-agent anti-PD-1 (n = 80 [74.1%]), followed by combination CTLA-4/PD-1 inhibitors (n = 19 [17.6%]). Three patients experienced long-term radiation-induced sequelae: 2 had esophageal stricture and 1 had bowel obstruction. No patients developed radiation-induced myelopathy. There was no association between receipt of ICI and development of any of these adverse events (p > 0.9). Similarly, ICI was not significantly associated with either LC (p = 0.3) or OS (p = 0.6). In the entire cohort, patients who received ICI prior to beginning SBRT had worse median survival, but ICI sequence with respect to SBRT was not significantly prognostic of either LC (p > 0.3) or OS (p > 0.07); instead, baseline performance status was most predictive of OS (HR 1.38, 95% CI 1.07-1.78, p = 0.012). CONCLUSIONS: Treatment regimens that combine ICIs before, concurrent with, and after SBRT for spine metastases are safe, with minimal risk for increased rates of long-term toxicity.

Predicting Resting Oral Commissure Tone Outcomes Following Masseter Nerve Transfer in Facial Reanimation.

Objective: To quantify the degree of oral commissure resting tone improvement in patients undergoing masseter to facial nerve transfer. Methods: A retrospective cohort study was completed in a tertiary academic medical practice. Consecutive cases of masseter nerve transfer patients within a patient database were evaluated from 6/2012 to 9/2017. Inclusion criteria were patients >18 years of age, with complete unilateral paralysis, receiving a masseter to facial nerve transfer, with at least 12 months of recovery, and possessing complete pre- and postoperative data. Patients were excluded if a simultaneous adjunctive procedure was performed so that tone could not be attributed to masseter transfer alone. The main outcome measure was the facial asymmetry index (FAI): the measured difference in distance between the medial canthus and oral commissure of the healthy and paralyzed sides. Results: Twenty-nine patients met inclusion and exclusion criteria and were further analyzed for this study. The oral commissure symmetry improved from 4.7 ± 2.8 mm preoperatively to 2.2 ± 2.3 mm postoperatively. In multivariate analysis, the preoperative FAI was the only significant predictive factor for improvement in commissure symmetry at rest (r = 0.589). This suggests that for each 1.0 mm of worse preoperatively oral commissure asymmetry, the improvement postoperatively was 0.6 mm. Age, gender, body mass index, side of paralysis, duration of paralysis, and recipient branch of facial nerve were not significant predictors in a multivariate analysis. Conclusion: Masseter to facial nerve transfer yields an estimated 60% correction in the oral commissure asymmetry. This estimation may be helpful in determining if adjunctive procedures should be utilized.

Perigeniculate arachnoid cysts and CSF fistulae of the fallopian canal: Histopathologic correlates of a rare clinical entity.

Cerebrospinal fluid (CSF) fistulae originating from the fallopian canal of the facial nerve is hypothesized to arise due to atypical patterns of subarachnoid space extension into the geniculate ganglion or more distal regions along the intratemporal course of the facial nerve, but its pathogenesis remains poorly understood. Although a rare etiology of CSF fistulae of the temporal bone, there are significant clinical ramifications due to the risk of recurrent meningitis, difficulty in identifying the anatomic location of the CSF leak, and technical challenges associated with surgical repair. We present three clinical cases of arachnoid cysts within the geniculate fossa with or without CSF fistulization and provide histopathologic correlates of this rare clinical phenomenon from a human temporal bone collection. The pediatric and adult patients presented suggest differential pathophysiologic mechanisms associated with CSF fistulae. Temporal bone histology reveals atypical patterns of subarachnoid space extension in the fallopian canal that may underlie arachnoid cyst formation and overt CSF leak from the geniculate region.

Characterization of Geriatric Dysphagia Diagnoses in Age-Based Cohorts.

OBJECTIVE: An aging population requires increased focus on geriatric otolaryngology. Patients aged ≥65 years are not a homogenous population, and important physiologic differences have been documented among the young-old (65-74 years), middle-old (75-84), and old-old (≥85). We aim to analyze differences in dysphagia diagnoses and swallowing-related quality-of-life among these age subgroups. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary care laryngology clinic. SUBJECTS AND METHODS: We identified chief complaint, diagnosis, and self-reported swallowing handicap (Eating Assessment Tool [EAT-10] score) of all new patients aged ≥65 years presenting to the Johns Hopkins Voice Center between April 2015 and March 2017. Dysphagia diagnoses were classified by physiologic etiology and anatomic source. Diagnostic categories and EAT-10 score were evaluated as functions of patient age and sex. RESULTS: Of 839 new patients aged ≥65 years, 109 (13.0%) reported a chief complaint of dysphagia and were included in this study. The most common dysphagia etiologies were neurologic and esophageal. Most common diagnoses were diverticula (15.6%), reflux (13.8%), and radiation induced (8.3%). Diverticula, cricopharyngeal hypertonicity, and radiation-induced changes were associated with higher EAT-10 score (P < .001). Significant differences by sex were found in anatomic source of dysphagia, as men and women were more likely to present with oropharyngeal and esophageal disease, respectively (P = .023). Dysphagia etiology and EAT-10 score were similar across age subgroups. CONCLUSION: Important differences among dysphagia diagnosis and EAT-10 score exist among patients aged ≥65 years. Knowledge of these differences may inform diagnostic workup, management, and further investigations in geriatric otolaryngology.