Search

5068 Background: Anti-PD-1/PD-L1 immune-checkpoint inhibitors (ICI) are now a standard of care in metastatic renal cell carcinoma (mRCC). Older adults were underrepresented in registration trials and given that immunological senescence may affect the anti-tumor activity of ICIs, there is uncertainty about the efficacy of ICIs in this population. Here we provide real world data on outcomes of older adults with mRCC treated with ICIs. Methods: Patients with mRCC treated with a PD-1/PD-L1 ICI either as monotherapy or as a combination treatment from 2000 to 2019 were included. Older adult was defined as ≥ 70-years at the time of ICI treatment. Descriptive statistics were summarized in means, medians and proportions. Efficacy was assessed by survival analysis, including overall survival (OS), time to treatment failure (TTF), and overall response rate (ORR). Multivariate analyses adjusted for imbalances in IMDC risk factors. P < 0.05 was considered statistically significant. Results: Of 1427 patients, 397 (28%) were older adults. Mean age of older vs. younger adults was 74 (70-92) vs. 60 (22-69) years. Groups were comparable in terms of gender (Female 28.5% vs. 26.1%, p = 0.36), rates of nephrectomy (21% vs. 18.3%, p = 0.24) and presence of sarcomatoid features (12.3% vs. 17.8%, p = 0.14). Proportion of IMDC risk-groups between older vs. younger adults were as follows: 15.4% vs. 18.2% for favorable, 61.2% vs. 59.1% for intermediate, and 23.4% vs. 22.7% for poor; there was no statistical difference (p = 0.55). ICI was used as 1st line in 40%, 2nd line in 48.5% and 3rd line in 11.5% patients; older adults were less likely to be treated with ICI in 1st line (32.2% vs. 43%, p < 0.01). In terms of survival, older adults had poorer median OS (25.1m vs. 30.8m, p < 0.01) but similar median TTF (6.9m vs. 6.9m, p = 0.40) compared to younger adults. In multivariate analyses, older age was not a predictor of either worse OS (aHR = 1.02, p = 0.86) or TTF (aHR = 0.95, p = 0.59). Older adults had a lower ORR compared to younger (24% vs. 31%, p = 0.01), which was mainly driven by responses in 1st line (31% vs. 44%, p = 0.02) and not observed in 2nd/3rd line (20% vs. 20%, p = 0.86). Conclusions: On multivariate analyses, older adults with mRCC treated with ICI had no difference in OS and TTF when compared to younger adults, despite having lower ORR in 1st line. Our data supports that older age is not an independent risk factor for survival; thus, treatment selection should not be based solely on chronological age.

In a previous study, we found interobserver agreement among 88 board-certified pathologists evaluating perineural invasion (PNI) in oral squamous cell carcinoma (OSCC) was fair, and participants most often used the following criteria: (1) tumor invading the perineurium, (2) tumor surrounding a nerve. In this study, we aimed to determine whether application of these most commonly used criteria may improve interobserver agreement. 512 pathologists were invited to participate in a web-based survey. Participants were asked to assess the presence/absence of PNI in a set of OSCC photomicrographs by applying each of the two criteria above. The survey was completed by 84 board-certified pathologists [mean age: 52 years (range 31–81), mean years in practice: 19 (range 1–56)]. Interobserver agreement was moderate (k = 0.46, 95% CI 0.45–0.46) when using definition #1 (tumor invading the perineurium) and fair (k = 0.24, 95% CI 0.23–0.25) when using definition #2 (tumor surrounding a nerve). By comparison, interobserver agreement was fair (k = 0.36, 95% CI 0.35–0.37) among phase 1 participants asked to evaluate these photomicrographs as they would in their pathology practice. Differences in kappa between definition #1 and phase 1, definition #2 and phase 2, and definition #1 and #2 were statistically significant (p

OBJECTIVE. To assess the impact of rural-urban residence on children with obstructive sleep-disordered breathing (SDB) who were candidates for tonsillectomy with or without adenoidectomy (TA). STUDY DESIGN. Retrospective cohort study. SETTING. Tertiary children’s hospital. METHODS. A cohort of otherwise healthy children aged 2 to 18 years with a diagnosis of obstructive SDB between April 2016 and December 2018 who were recommended TA were included. Rural-urban designation was defined by ZIP code approximation of rural-urban commuting area codes. The main outcome was association of rurality with time to TA and loss to follow-up using Cox and logistic regression analyses. RESULTS. In total, 213 patients were included (mean age 6 ± 2.9 years, 117 [55%] male, 69 [32%] rural dwelling). Rural-dwelling children were more often insured by Medicaid than private insurance (P < .001) and had a median driving distance of 74.8 vs 16.8 miles (P < .001) compared to urban-dwelling patients. The majority (94.9%) eventually underwent recommended TA once evaluated by an otolaryngologist. Multivariable logistic regression analysis did not reveal any significant predictors for loss to follow-up in receiving TA. Cox regression analysis that adjusted for age, sex, insurance, and race showed that rural-dwelling patients had a 30% reduction in receipt of TA over time as compared to urban-dwelling patients (hazard ratio, 0.7; 95% CI, 0.50-0.99). CONCLUSION. Rural-dwelling patients experienced longer wait times and driving distance to TA. This study suggests that rurality should be considered a potential barrier to surgical intervention and highlights the need to further investigate geographic access as an important determinant of care in pediatric SDB.

OBJECTIVE. Pathologic extranodal extension (ENE) is an important adverse feature for human papillomavirus (HPV)–negative head and neck squamous cell carcinoma (HNSCC), but the prognostic significance of microscopic ENE (ENE(mi)) and role of adjuvant concurrent chemoradiation (CRT) for ENE(mi) remain unclear. This study evaluates (1) the prognostic significance of ENE(mi) in HPV-negative HNSCC and (2) whether adjuvant CRT is associated with improved overall survival (OS) for these patients. STUDY DESIGN. Retrospective cohort study. SETTING. Commission on Cancer (CoC)–accredited facilities. METHODS. This retrospective cohort study included patients in the National Cancer Database from 2009 to 2015 with pathologic node-positive (pN+) HPV-negative HNSCC with either pathologic ENE(mi) or no ENE who had undergone margin-negative surgery. The association of ENE(mi) with OS was evaluated using Cox proportional hazard analyses. Analyses were repeated in patients with ENE(mi) receiving adjuvant therapy to evaluate the association of adjuvant CRT with OS. RESULTS. We included 5483 patients with pN+ HPV-negative HNSCC, of whom 24% had ENE(mi). On multivariable analysis, ENE(mi) was associated with decreased OS relative to no ENE (adjusted hazard ratio [aHR], 1.43; 95% CI, 1.28-1.59). Among patients with ENE(mi) who received ≥60 Gy of adjuvant radiation therapy (RT) (n = 617), adjuvant CRT was not associated with improved OS relative to RT (aHR, 0.91; 95% CI, 0.66-1.27). CONCLUSION. For patients with HPV-negative HNSCC, pN+ with ENE(mi) is associated with worse OS than pN+ without ENE. However, for patients with ENE(mi), concurrent CRT is not associated with improved OS relative to RT. The optimal adjuvant paradigm for ENE(mi) requires additional investigation.

Background Cabozantinib is approved for metastatic renal cell carcinoma (mRCC) based on the METEOR and CABOSUN trials. However, real‐world effectiveness and dosing patterns of cabozantinib are not well characterized. Methods Patients with mRCC treated with cabozantinib between 2011 and 2019 were identified and stratified using the International mRCC Database Consortium (IMDC) risk groups. First‐ (1L), second‐ (2L), third‐ (3L), and fourth‐line (4L) overall response rate (ORR), time to treatment failure (TTF), and overall survival (OS) were analyzed. Dose reduction rates and their association with TTF and OS were determined. Results A total of 413 patients were identified. The ORRs across 1L to 4L were 32%, 26%, 25%, and 29%, respectively, and the median TTF rates were 8.3, 7.3, 7.0, and 8.0 months, respectively. The median OS (mOS) rates in 1L to 4L were 30.7, 17.8, 12.6, and 14.9 months, respectively. For patients treated with 1L PD(L)1 combination agent (n = 31), 2L cabozantinib had ORR of 22%, median TTF of 5.4 months, and mOS of 17.4 months. About 50% (129/258) of patients required dose reductions. The TTF and mOS were significantly longer for patients who required dose reduction vs. patients who did not, with an adjusted hazard ratio of 0.37 (95% CI 0.202–0.672, p, Cabozantinib demonstrates activity for use in real‐world patients with metastatic renal cell carcinoma across the first‐ to fourth‐line treatment settings.

The aim of this study was to identify factors that are associated with the occurrence of pneumonia in patients with head and neck cancer (HNC) after treatment.PubMed, Scopus, OVID, and Cochrane Library from inception to November 26, 2019.A systematic review in accordance with the PRISMA guidelines and an assessment of bias were performed. Included studies reported on the risk factors of pneumonia development after HNC treatment via odds ratios and subdistribution hazard ratios from regression analysis.Fifteen studies were included, comprising 30,962 patients with a mean age of 70 years (range, 19-95 years). Of these, 71.6% are male. The results of our study indicate that the following were independent risk factors contributing to the development of pneumonia: male sex, habitual alcohol consumption, poor oral hygiene before treatment, pretreatment dysphagia, hypopharynx and nasopharynx tumor sites, use of radiotherapy with or without chemotherapy versus surgery alone, addition of chemotherapy to radiotherapy, reirradiation, neck dissection, increased duration of tracheotomy, and use of sedatives for sleeping.Multiple patient-, tumor-, and treatment-specific risk factors were identified in predicting pneumonia. Recognition of these risk factors early on may help prevent or at least detect pneumonia in this vulnerable group of patients.

Pathologic extranodal extension (pENE) impacts treatment planning and is an important prognostic indicator for patients with head and neck squamous cell carcinoma (HNSCC). Computed tomography (CT) is a commonly used modality for assessment of radiographic ENE (rENE). To determine the predictive value of CT-identified rENE in predicting pENE, we performed a systematic review through a search of 4 databases (PubMed, Scopus, Cochrane, and OVID). Meta-analysis of diagnostic performance based on human papillomavirus (HPV) status was conducted. For HPV-negative HNSCC, pooled sensitivity, specificity, and accuracy were 60.6%, 93.3%, and 82.6%, respectively. Overall positive predictive value (PPV) was 82.7%. For HPV-positive HNSCC, pooled sensitivity, specificity, and accuracy were 77.7%, 72.2%, and 63.8%, respectively. Overall PPV was 68.6%. Significant differences were observed in diagnostic performance parameters between the two cohorts. The radiographic characteristics of HPV-positive and HPV-negative nodal metastases in HNSCC differ and radiographic evaluation of ENE in HPV-positive nodes is challenging. Development of refined imaging characteristics of HPV-positive nodes is needed to improve diagnostic performance.

Oral potentially malignant disorders (OPMDs) may have varying degrees of oral epithelial dysplasia (OED). Traditional grading schemes separate OED into three-tiers (mild, moderate, and severe). Alternatively, a binary grading system has been previously proposed that stratifies OED into low-risk and high-risk categories based on a quantitative threshold of dysplastic pathologic characteristics. This systematic review evaluates the predictive value of a binary OED grading system and examines agreement between pathologists. This meta-analysis queried 4 databases (PubMed, Ovid-MEDLINE, Cochrane, and SCOPUS) and includes 4 studies evaluating binary OED grading systems. Meta-analysis of proportions and correlations was performed to pool malignant transformation rates (MTR), risk of malignant transformation between OED categories, and measures of interobserver agreement. Pooled analysis of 629 lesions from 4 different studies found a six-time increased odds of malignant transformation in high-risk lesions over low-risk lesions [odds ratio (OR) 6.14, 95% 1.18–15.38]. Reported ORs ranged from 2.8 to 22.4. The overall MTR was 26.8%, with the high-risk and low-risk lesions having MTRs of 57.9% (95% CI 0.386–0.723) and 12.7% (95% CI − 0.210 to 0.438), respectively. Pooled unweighted interobserver kappa values for the binary grading system and three-tiered system were 0.693 (95% CI 0.640–0.740) and 0.388 (95% CI 0.195–0.552), respectively. Binary grading of OED into low-risk and high-risk categories may effectively determine malignant potential, with improved interobserver agreement over three-tiered grading. Improved grading schemes of OED may help guide management (watchful waiting vs. excision) of these OPMDs.

Objective.To determine the prevalence of hearing loss (HL) in patients with ankylosing spondylitis (AS) and to describe frequency-specific hearing threshold changes in this patient population compared to patients without AS.Methods.A systematic review querying 4 databases (PubMed, OVID Medline, Scopus, Cochrane) was performed to identify studies evaluating HL in patients with AS. Metaanalysis was performed to identify overall prevalence rate and OR of HL, as well as to compare mean differences in frequency-specific hearing thresholds between patients with and without AS.Results.Our metaanalysis included 14 studies and 1083 patients (598 with AS vs 485 without AS). The pooled prevalence of HL in patients with AS was 42.4% (95% CI 29.2–56.2). Patients with AS had a significantly higher OR of HL than patients without AS (OR 4.65, 95% CI 2.73–7.91). Mean differences in pure-tone hearing thresholds ranged from 0–5 decibels (dB) for frequencies of 0.25–4 kHz, and from 5–15 dB for frequencies of 6–16 kHz.Conclusion.Patients with AS have higher odds of having HL than patients without AS. The AS population also presents with significantly impaired hearing thresholds across all conventional and extended pure-tone frequencies. This may manifest as slight to moderate HL. Results of this systematic review might justify increased attention to audiologic manifestations of patients with AS.

Introduction This study aims to determine whether advanced ROS1 gene-rearranged NSCLC (ROS1+ NSCLC) has a higher than expected thromboembolic event (TEE) rate. Methods Venous and arterial TEEs within ±365 days of diagnosis of ROS1+, ALK+, EGFR+, or KRAS+ advanced NSCLC at five academic centers in the United States and China were captured (October 2002–April 2018). The primary endpoint was incidence of TEE in ROS1+ compared to anaplastic lymphoma kinase (ALK)+, EGFR+, and KRAS+ NSCLC within ±90 days of diagnosis. Logistic regression was used to assess if the odds of TEE differed among oncogene drivers. Results Eligible data from 95 ROS1+, 193 ALK+, 300 EGFR+, and 152 KRAS+ NSCLC patients were analyzed. The incidence rate of TEE was 34.7% (n = 33), 22.3% (n = 43), 13.7% (n = 41), and 18.4% (n = 28), respectively. In univariate analysis, the odds of a TEE in ROS1+ NSCLC were higher than ALK+, EGFR+, and KRAS+ cohorts. In multivariable analysis, the odds of a TEE were significantly higher for ROS1+ compared to EGFR+ and KRAS+ cohorts, the odds ratio (OR) was 2.44, with a 95% confidence interval of 1.31–4.57 (p = 0.005), and OR: 2.62, with a 95% confidence interval of 1.26–5.46 (p = 0.01), respectively. Although numerically superior, the odds for a TEE with ROS1+ compared to ALK+ was not statistically significant (OR: 1.45, p = 0.229). Overall survival was not significantly different in patients with or without TEE within ±90 days of diagnosis in the overall study cohort or within each molecular group. Conclusions The risk of peridiagnostic TEEs is significantly elevated in patients with advanced ROS+ NSCLC compared to EGFR+ and KRAS+ cases. TEE risk may be similarly elevated in ALK+ NSCLC.

To characterize the relationship between dizziness severity and cognitive dysfunction in vestibular migraine (VM) patients.Dizziness Handicap Inventory (DHI) and Cognitive Failures Questionnaire (CFQ) scores were compared pre- and post-treatment in a cohort of definite VM patients who underwent evaluation in a multidisciplinary clinic from 2016 to 2020.44 patients were included. DHI reduction of 11.96 (SD 11.49) (p 0.001) from an initial mean of 58.36 (22.05) and CFQ reduction of 4.57 (12.20) (p = 0.017) from an initial mean of 47.66 (19.12) were demonstrated. Both pre- and post-treatment DHI scores correlated with pre- and post-treatment CFQ scores (r = 0.537, p 0.001 and r = 0.667, p 0.001, respectively). Change in DHI score correlated with change in CFQ score (r = 0.351, p = 0.019).Cognitive dysfunction in VM patients is correlated with dizziness severity. The DHI may fail to thoroughly assess cognitive dysfunction in VM patients. Additionally, multidisciplinary treatment of VM reduces both dizziness severity and cognitive dysfunction.

Given the rapidly evolving nature of the field, the current state of “high-risk” head and neck cutaneous squamous cell carcinoma (HNcSCC) is poorly characterized. Narrative review of the epidemiology, diagnosis, workup, risk stratification, staging and treatment of high-risk HNcSCC. Clinical and pathologic risk factors for adverse HNcSCC outcomes are nuanced (e.g., immunosuppression and perineural invasion). Frequent changes in adverse prognosticators have outpaced population-based registries and the variables they track, restricting our understanding of the epidemiology of HNcSCC and inhibiting control of the disease. Current heterogeneous staging and risk stratification systems are largely derived from institutional data, compromising their external validity. In the absence of staging system consensus, tumor designations such as “high risk” and “advanced” are variably used and insufficiently precise to guide management. Evidence guiding treatment of high-risk HNcSCC with curative intent is also suboptimal. For patients with incurable disease, an array of trials are evaluating the impact of immunotherapy, targeted biologic therapy, and other novel agents. Population-based registries that broadly track updated, nuanced, adverse clinicopathologic risk factors, and outcomes are needed to guide development of improved staging systems. Design and development of randomized controlled trials (RCTs) in advanced-stage HNcSCC populations are needed to evaluate (1) observation, sentinel lymph node biopsy, or elective neck dissection for management of the cN0 neck, (2) indications for surgery plus adjuvant radiation versus adjuvant chemoradiation, and (3) the role of immunotherapy in treatment with curative intent. Considering these knowledge gaps, the authors explore a potential high-risk HNcSCC treatment framework.

Objective The hobnail variant of papillary thyroid carcinoma (HVPTC) has emerged as a rare and aggressive variant of papillary thyroid carcinoma (PTC). We aim to determine the prevalence and clinicopathologic factors of HVPTC. Methods A systematic review of the literature for studies examining HVPTC was performed. Four databases (PubMed, Scopus, OVID, Cochrane library) were queried from inception of databases through March 20th, 2020. Results Sixteen studies with 124 cases of HVPTC were included. The mean age for all patients was 52.3 years. HVPTC had a prevalence of 1.08% out of all PTC cases, with a mean tumor size of 3.1 cm. In 62% and 50% of cases, lymphovascular invasion and extrathyroidal extension were present, respectively. Follow-up data, with a mean of 49.9 months, revealed a 66% rate of lymph node metastasis and 23% rate of distant metastasis. Tumors with ≥30% hobnail morphology had a 2.6-fold increased odds of developing lymph node metastasis compared with

The COVID‐19 pandemic has had a significant impact on many aspects of head and neck cancer (HNC) care. The uncertainty and stress resulting from these changes has led many patients and caregivers to turn to HNC advocacy groups for guidance and support. Here we outline some of the issues being faced by patients with HNC during the current crisis and provide examples of programs being developed by advocacy groups to address them. We also highlight the increased utilization of these organizations that has been observed as well as some of the challenges being faced by these not‐for‐profit groups as they work to serve the head and neck community.

To evaluate the treatment efficacy of transcutaneous electrical nerve stimulation (TENS) in patients with obstructive sleep apnea (OSA).Primary studies were identified though PubMed, Scopus, OVID, and Cochrane Library.Systematic review was conducted by querying databases for articles published through July 2019. The search identified randomized controlled trial, randomized comparison, or observational studies pertaining to TENS treatment for OSA. Meta-analysis was performed on pre- and posttreatment apnea-hypopnea index (AHI), mean oxygen saturation (SaOLiterature search identified 10 studies that reported sufficient outcome measures to be considered for analysis. A total of 198 patients were identified with a mean age of 50.9 years with a male to female ratio of 1.6:1. Average body mass index (BMI) of the cohort was 29.8 kg/mThe TENS treatment of upper airway dilator muscles resulted in reduction of AHI in patients with OSA. However, its effects on SaO

Background Greater auricular nerve (GAN) sacrifice can alter sensation; however, the impact on quality of life (QoL) is unclear. Objective The aim of this study was to evaluate patients' QoL following GAN sacrifice versus preservation. Methods Patients who underwent parotidectomy from 2010 to 2019 at a single institution completed two QoL surveys. Results between GAN-sacrificed versus preserved cohorts and short (≤ 1 year) versus long-term (> 1 year) follow-up were compared. Results Of 404 patients, 67 with known GAN status completed the surveys. GAN-sacrificed patients more frequently experienced sensation loss of the lobule and concha than GAN-preserved patients (P = .042 and P = .041, respectively). Interference with daily activities or amount of regained sensation was not different based on GAN status. Short-term follow-up patients had a higher number of symptoms and affected areas than long-term follow-up patients (P = .014 and P = .002, respectively). Conclusion GAN sacrifice leads to sensation loss of the lobule and concha; however, it does not significantly impair QoL.

Background Migraine is characterized by a collection of neurological symptoms in the absence of injury or damage. However, several common preclinical migraine models require significant damage to the skull to stimulate the dura mater, the likely source of afferent signaling leading to head pain. The goal of this study was to determine whether dural stimulation can be performed in mice using an injection that does not cause injury or damage. Methods Using mice, injections of stimuli were administered to the dura mater through the soft tissue at the intersection between the lambdoidal and sagittal sutures. This technique did not require a permanent cannula nor did it cause damage to the skull or dura. Following injection of noxious stimuli, migraine-like behaviors were measured including cutaneous allodynia and facial grimace. The retrograde tracer fluorogold was applied onto the dura using the same injection technique to label trigeminal ganglion cell bodies, which were then testing in vitro using patch-clamp electrophysiology. Results Dural injection of allyl-isothiocyanate, low pH, interleukin-6, or inflammatory soup but not vehicles, led to cephalic/extracephalic allodynia. Facial grimace responses were also observed with allyl-isothiocyanate, pH 6.0, and interleukin-6. Stimulation with interleukin-6 causes priming to normally subthreshold pH 7.0 stimulation of the dura following resolution of the initial interleukin-6 behavior. Systemic injection of sumatriptan at the time of dural stimulation with inflammatory soup decreased the resulting cutaneous hypersensitivity. Trigeminal ganglion cell bodies retrogradely labeled from the dura had low pH-evoked currents similar to those generated by acid-sensing ion channels. Conclusion Non-invasive dural stimulation in mice can be used as a model of migraine in the absence of injury.

BACKGROUND: In metastatic renal-cell carcinoma (mRCC), recent data have shown efficacy of first-line ipilimumab and nivolumab (ipi-nivo) as well as immuno-oncology (IO)/vascular endothelial growth factor (VEGF) inhibitor combinations. Comparative data between these strategies are limited.OBJECTIVE: To compare the efficacy of ipi-nivo versus IO-VEGF (IOVE) combinations in mRCC, and describe practice patterns and effectiveness of second-line therapies.DESIGN, SETTING, AND PARTICIPANTS: Using the International Metastatic Renal-cell Carcinoma Database Consortium (IMDC) dataset, patients treated with any first-line IOVE combination were compared with those treated with ipi-nivo.INTERVENTION: All patients received first-line IO combination therapies.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: First- and second-line response rates, time to treatment failure (TTF), time to next treatment (TNT), and overall survival (OS) were analysed. Hazard ratios were adjusted for IMDC risk factors.RESULTS AND LIMITATIONS: In total, 113 patients received IOVE combinations and 75 received ipi-nivo. For IOVE combinations versus ipi-nivo, first-line response rates were 33% versus 40% (between-group difference 7%, 95% confidence interval [CI] -8% to 22%, p = 0.4), TTF was 14.3 versus 10.2 mo (p = 0.2), TNT was 19.7 versus 17.9 mo (p = 0.4), and median OS was immature but not statistically different (p = 0.17). Adjusted hazard ratios for TTF, TNT, and OS were 0.71 (95% CI 0.46-1.12, p = 0.14), 0.65 (95% CI 0.38-1.11, p = 0.11), and 1.74 (95% CI 0.82-3.68, p = 0.14), respectively. Sixty-four (34%) patients received second-line treatment. In patients receiving subsequent VEGF-based therapy, second-line response rates were lower in the IOVE cohort than in the ipi-nivo cohort (15% vs 45%; between-group difference 30%, 95% CI 3-57%, p = 0.04; n = 40), though second-line TTF was not significantly different (3.7 vs 5.4 mo; p = 0.4; n = 55). Limitations include the study's retrospective design and sample size.CONCLUSIONS: There were no significant differences in first-line outcomes between IOVE combinations and ipi-nivo. Most patients received VEGF-based therapy in the second line. In this group, second-line response rate was greater in patients who received ipi-nivo initially.PATIENT SUMMARY: There were no significant differences in key first-line outcomes for patients with metastatic renal-cell carcinoma receiving immuno-oncology/vascular endothelial growth factor inhibitor combinations versus ipilimumab and nivolumab.

Importance The American Joint Committee on Cancer staging system (Cancer Staging Manual, 8th Edition) for head and neck squamous cell carcinoma (HNSCC) now categorizes human papillomavirus (HPV)–negative HNSCC in a single positive lymph node smaller than 3 cm with pathologic extranodal extension (ENE) as N2a. The standard of care for pathologic ENE is adjuvant chemoradiation therapy (CRT). Whether adding chemotherapy concurrent with adjuvant radiation therapy improves survival in this clinical scenario is unknown. Objective To assess whether adjuvant CRT relative to radiation therapy alone is associated with improved survival among patients with pN2a HPV-negative HNSCC with ENE. Design, Setting, and Participants This retrospective cohort study included 504 patients with pN2a HPV-negative HNSCC with ENE who had undergone margin-negative surgery and adjuvant therapy. The patients were identified from the National Cancer Database from January 1, 2004, to December 31, 2015. Statistical analyses were conducted from September 1, 2019, to April 16, 2020. Main Outcomes and Measures The primary end point was overall survival. The association of adjuvant CRT with overall survival was analyzed using univariate and multivariate Cox proportional hazards regression analyses. Planned subset analyses were conducted in patients younger than 70 years with no comorbidities (the subset most likely to be eligible for a clinical trial of cisplatin-based chemoradiation) and in patients with pT3/T4 disease classification. Results Of 504 patients (mean [SD] age, 60.5 [12.7] years; 319 [63.3%] men; 434 [86.1%] White) with pN2a HPV-negative HNSCC with ENE who had undergone margin-negative surgery and adjuvant therapy, 298 patients (59.1%) received adjuvant CRT. For the overall cohort of patients with pN2a ENE, adjuvant CRT was not associated with improved overall survival relative to adjuvant radiation therapy alone in a multivariate analysis (adjusted hazard ratio, 0.98; 95% CI, 0.74-1.30). Adjuvant CRT was still not associated with improved overall survival in a subset analysis of 304 patients younger than 70 years with no comorbidities (adjusted hazard ratio, 0.98; 95% CI, 0.66-1.45) nor in a subset of 220 patients with pT3/T4 disease classification (adjusted hazard ratio, 1.03; 95% CI, 0.70-1.54). Conclusions and Relevance This study found that for patients with pN2a HPV-negative HNSCC with ENE who underwent margin-negative surgery and adjuvant therapy, adding chemotherapy concurrent with adjuvant radiation therapy was not associated with improved overall survival. Additional research is necessary to identify the optimal treatment paradigm for this clinical scenario.

Importance Preservation of endolymphatic fluids, maintenance of a fluid-filled vestibule, and preservation of the cochlear nerve and its vasculature are believed to be necessary to retaining hearing after an inner-ear operation. However, some studies have reported no hearing loss despite the violation of the vestibule, questioning the importance of maintaining a fluid-filled vestibule in preserving hearing. Objective To report on the preservation of hearing after a complete labyrinthectomy for Meniere disease and after disruption of the vestibule. Evidence Review This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. A search of PubMed, Scopus, Ovid, and Cochrane Library databases was conducted to identify English-language articles on hearing preservation after labyrinthectomy, published from 1947 through December 11, 2019. The search strategy used a combination of boolean operators and included the following Medical Subject Heading terms and keywords: hearing preservation, labyrinth surgery, labyrinthectomy, vestibule violation, vestibule disruption, translabyrinthine approach, schwannoma removal, and semicircular canal ablation. Studies that included disruption of the vestibule and hearing preservation were included. Findings This systematic review identified 10 studies with 10 patients who underwent surgical removal of cholesteatoma or vestibular schwannoma and displayed postoperative hearing preservation. This study also reported on 1 patient with Meniere disease who retained hearing after undergoing a complete labyrinthectomy. Among these 11 patients, the mean (range) age was 45.1 (27-55) years, and 8 patients (73%) were women. Multiple theories exist that explain the mechanism behind hearing preservation, such as sealing of the ductus reuniens or closure of the remaining vestibule. Conclusions and Relevance This systematic review describes a set of patients who did not experience hearing loss after a labyrinthectomy or surgical violation of the vestibule, which seems to contradict prevailing principles for retaining hearing after inner-ear surgical procedures. This finding suggests that hearing preservation is possible after labyrinthine destruction despite the absence of a fluid-filled vestibule and that other mechanisms, such as occlusion of the ductus reuniens with granulation tissue or bone dust, may be sufficient to achieve that outcome.

Cancers that arise in the head and neck region are comprised of a heterogeneous group of malignancies that include carcinogen- and human papillomavirus (HPV)-driven mucosal squamous cell carcinoma as well as skin cancers such as cutaneous squamous cell carcinoma, basal cell carcinoma, melanoma, and Merkel cell carcinoma. These malignancies develop in critical areas for eating, talking, and breathing and are associated with substantial morbidity and mortality despite advances in treatment. Understanding of advances in the management of these various cancers is important for all multidisciplinary providers who care for patients across the cancer care continuum. Additionally, the recent Coronavirus Disease 2019 (COVID-19) pandemic has necessitated adaptations to head and neck cancer care to accommodate the mitigation of COVID-19 risk and ensure timely treatment. This review explores advances in diagnostic criteria, prognostic factors, and management for subsites including head and neck squamous cell carcinoma and the various forms of skin cancer (basal cell carcinoma, cutaneous squamous cell carcinoma, Merkel cell carcinoma, and melanoma). Then, this review summarizes emerging developments in immunotherapy, radiation therapy, cancer survivorship, and the delivery of care during the COVID-19 era.

645 Background: With the approval of immune-checkpoint inhibitors (ICI) as first and second line agents for treating metastatic renal cell carcinoma (RCC), immune-related adverse events (irAE) are a growing concern. In this study, we present the safety profile and outcomes of 90 patients with RCC treated at two centers, including a university (UT Southwestern/Clements University Hospital) and a county hospital (UT Southwestern/Parkland). Methods: All patients with RCC treated with ICI were identified from 2013 to January 31, 2018. We examined the incidence of any treatment-related adverse events and “select” irAEs and evaluated their impact on patient outcomes and therapeutic decisions. Kaplan-Meier methods and Cox proportional hazards regression models were used to compare overall survival (OS) and time to next therapy (TTNT) by the presence of irAEs. Results: Of 90 patients treated with ICI, 65 (72.2%) patients experienced adverse events, most commonly fatigue (37.8%), nausea (14%), and decreased appetite (12.2%). Select irAEs were seen in 38 (42.2%) with the most common irAEs involving the skin (15.6%), gastrointestinal tract (14%), endocrine organs (11%), and lungs (7.8%). There were 15 (16.7%) grade III/IV irAEs resulting in cessation of therapy for 12 (13.3%) patients. The median OS was 35.9 (95% CI: 24.3-not reached) and 26.5 months (95% CI: 10.2-28.8; p = 0.002) for patients with and without irAEs, respectively. The median TTNT was 17.8 (95% CI: 11.3-29.3) and 6.6 months (95% CI: 4.5-9.6; p = 0.002) for patients with and without irAEs, respectively. In multivariate analysis of irAE status and Heng prognostic score, irAEs were associated with improved OS, HR 0.376 (95% CI 0.179–0.792; p = 0.010) and TTNT, HR 0.482 (95% CI 0.280–0.829; p = 0.008). Conclusions: ICI in RCC is well tolerated with only 16.7% of patients experiencing an adverse event resulting in cessation of therapy. The development of an irAE correlated with both an improved median OS as well as median TTNT, a benefit that persisted after multivariate analysis including Heng prognostic scoring. These findings suggest that the development of irAEs may be an independent positive prognostic factor in patients with RCC treated with ICI.

584 Background: In mRCC, ipilimumab and nivolumab (ipi-nivo) is a 1L treatment option. Recent data have also shown efficacy of 1L PD(L)1-VEGF (PV) inhibitor combinations. The efficacy of these two strategies has not been compared. Methods: Using the IMDC dataset, patients (pts) treated with any 1L PV combination were compared to those treated with ipi-nivo. Multivariable Cox regression analysis was performed to control for imbalances in IMDC risk factors. Results: 164 pts received 1L IO combination therapy: 104 treated with PV combinations and 60 with ipi-nivo. Baseline characteristics and IMDC risk factors were comparable between groups (Table). When comparing PV combinations vs ipi-nivo, 1L response rates (RR) were 30% vs 39% (p = 0.29), time to treatment failure (TTF) was 13.2 (95% CI 8.3-16.1) vs 8.5 months (95% CI 5.7-14.0, p = 0.31), and median overall survival (OS) was not reached (NR) (95% CI 19.7-NR) vs NR (95% CI 27.6-NR, p = 0.39). When adjusted for IMDC risk factors, the hazard ratio (HR) for TTF was 0.77 (95% CI 0.44-1.35, p = 0.36) and the HR for death was 0.94 (95% CI 0.33-2.71, p = 0.91). Similar results were seen when restricting the cohort to IMDC intermediate/poor risk pts only. In pts receiving subsequent VEGF TKI monotherapy, second-line (2L) RR (13% vs 45%, p = 0.07) and TTF (5.5 vs 5.4 months, p = 0.80) for PV combinations (n = 15) vs ipi-nivo (n = 20) were not significantly different. Conclusions: There does not appear to be a superior 1L IO combination strategy in mRCC, as PV combinations and ipi-nivo have comparable RR, TTF and OS. Although there is a trend towards differences in RR, there does not appear to be a significant difference in TTF for patients receiving 2L VEGF TKI therapy. [Table: see text]