Efficacy and Safety of Switching to the 2-Drug Regimen Dolutegravir/Lamivudine Versus Continuing a 3- or 4-Drug Regimen for Maintaining Virologic Suppression in Adults Living With Human Immunodeficiency Virus 1 (HIV-1): Week 48 Results From the Phase 3, Noninferiority SALSA Randomized Trial.

BACKGROUND: In TANGO, switching to dolutegravir/lamivudine (DTG/3TC) demonstrated long-term noninferior efficacy vs continuing tenofovir alafenamide-based regimens in treatment-experienced adults with HIV-1. The phase 3 SALSA study evaluated efficacy and safety of switching to DTG/3TC compared with continuing various 3-/4-drug current antiretroviral regimens (CARs). METHODS: Adults with HIV-1 RNA <50 copies/mL and no previous virologic failure were randomized (1:1, stratified by baseline third agent class) to switch to once-daily fixed-dose combination DTG/3TC or continue CAR (primary endpoint: proportion of participants with HIV-1 RNA ≥50 copies/mL at week 48; Snapshot, intention-to-treat-exposed population, 5% noninferiority margin). RESULTS: Overall, 493 adults (39% women; 39% aged ≥50 years; 19% African American/African heritage; 14% Asian) were randomized to switch to DTG/3TC (n = 246) or continue CAR (n = 247). At week 48, 1 (0.4%) participant in the DTG/3TC group and 3 (1.2%) in the CAR group had HIV-1 RNA ≥50 copies/mL (Snapshot), demonstrating noninferiority (adjusted difference, -0.8%; 95% CI, -2.4%, .8%). Zero participants met confirmed virologic withdrawal criteria; therefore, no resistance testing was performed. Drug-related adverse events were more frequent with DTG/3TC (20%) than CAR (6%) through week 48 but comparable post-week 24 (5% vs 2%, respectively). Proximal tubular renal function and bone turnover biomarkers improved with DTG/3TC. Both groups had generally minimal changes in lipids and inflammatory biomarkers. CONCLUSIONS: Switching to DTG/3TC was noninferior to continuing CAR for maintaining virologic suppression at week 48 with no observed resistance, supporting the efficacy, good safety, and high barrier to resistance of DTG/3TC. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov, NCT04021290.

Phase I study of nab-paclitaxel-based induction followed by nab-paclitaxel-based concurrent chemotherapy and re-irradiation in previously treated head and neck squamous cell carcinoma.

BACKGROUND: Recurrent head and neck squamous cell carcinoma (HNSCC) is associated with poor overall survival (OS). Prior studies suggested incorporation of nab-paclitaxel (A) may improve outcomes in recurrent HNSCC. METHODS: This Phase I study evaluated induction with carboplatin and A followed by concomitant FHX (infusional 5-fluorouracil, hydroxyurea and twice-daily radiation therapy administered every other week) plus A with cohort dose escalation ranging from 10-100 mg/m2 in recurrent HNSCC. The primary endpoint was maximally tolerated dose (MTD) and dose-limiting toxicity (DLT) of A when given in combination with FHX (AFHX). RESULTS: Forty-eight eligible pts started induction; 28 pts started AFHX and were evaluable for toxicity. Two DLTs occurred (both Grade 4 mucositis) at a dose level 20 mg/m2. No further DLTs were observed with subsequent dose escalation. The MTD and recommended Phase II dose (RP2D) of A was 100 mg/m2. CONCLUSIONS: In this Phase I study, the RP2D of A with FHX is 100 mg/m2 (AFHX). The role of re-irradiation with immunotherapy warrants further investigation. CLINICAL TRIAL INFORMATION: This clinical trial was registered with ClinicalTrials.gov identifier: NCT01847326.

Plerixafor for the Treatment of WHIM Syndrome.

WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis), a primary immunodeficiency disorder involving panleukopenia, is caused by autosomal dominant gain-of-function mutations in CXC chemokine receptor 4 (CXCR4). Myelokathexis is neutropenia caused by neutrophil retention in bone marrow. Patients with WHIM syndrome are often treated with granulocyte colony-stimulating factor (G-CSF), which can increase neutrophil counts but does not affect cytopenias other than neutropenia. In this investigator-initiated, open-label study, three severely affected patients with WHIM syndrome who could not receive G-CSF were treated with low-dose plerixafor, a CXCR4 antagonist, for 19 to 52 months. Myelofibrosis, panleukopenia, anemia, and thrombocytopenia were ameliorated, the wart burden and frequency of infection declined, human papillomavirus-associated oropharyngeal squamous-cell carcinoma stabilized, and quality of life improved markedly. Adverse events were mainly infections attributable to the underlying immunodeficiency. One patient died from complications of elective reconstructive surgery. (Funded by the National Institutes of Health.).

Prospective study evaluating dynamic changes of cell-free HPV DNA in locoregional viral-associated oropharyngeal cancer treated with induction chemotherapy and response-adaptive treatment.

BACKGROUND: Human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) has a favorable prognosis which has led to efforts to de-intensify treatment. Response-adaptive de-escalated treatment is promising, however improved biomarkers are needed. Quantitative cell-free HPV-DNA (cfHPV-DNA) in plasma represents an attractive non-invasive biomarker for grading treatment response and post-treatment surveillance. This prospective study evaluates dynamic changes in cfHPV-DNA during induction therapy, definitive (chemo)radiotherapy, and post-treatment surveillance in the context of risk and response-adaptive treatment for HPV + OPC. METHODS: Patients with locoregional HPV + OPC are stratified into two cohorts: High risk (HR) (T4, N3, [Formula: see text] 20 pack-year smoking history (PYH), or non-HPV16 subtype); Low risk (LR) (all other patients). All patients receive induction chemotherapy with three cycles of carboplatin and paclitaxel. LR with ≥ 50% response receive treatment on the single-modality arm (minimally-invasive surgery or radiation alone to 50 Gy). HR with ≥ 50% response or LR with ≥ 30% and < 50% response receive treatment on the intermediate de-escalation arm (chemoradiation to 50 Gy with cisplatin). All other patients receive treatment on the regular dose arm with chemoradiation to 70 Gy with concurrent cisplatin. Plasma cfHPV-DNA is assessed during induction, (chemo)radiation, and post-treatment surveillance. The primary endpoint is correlation of quantitative cfHPV-DNA with radiographic response. DISCUSSION: A de-escalation treatment paradigm that reduces toxicity without compromising survival outcomes is urgently needed for HPV + OPC. Response to induction chemotherapy is predictive and prognostic and can select candidates for de-escalated definitive therapy. Assessment of quantitative cfHPV-DNA in the context of response-adaptive treatment of represents a promising reliable and convenient biomarker-driven strategy to guide personalized treatment in HPV + OPC. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov on October 1st, 2020 with Identifier: NCT04572100 .

Laryngeal and pharyngeal actinomycosis: a systematic review and report of 3 cases.

INTRODUCTION: Actinomycosis is a granulomatous infection that rarely involves the larynx or pharynx. Three cases of actinomycosis of the larynx or pharynx from our institution were reviewed and a systematic literature review was performed to better define surgical management, antibiotic therapy, risk factors, and incidence of recurrence or complications. MATERIALS AND METHODS: PubMed/Medline, Cochrane, Embase, and Google Scholar were searched on November 30, 2021 using the terms "laryngeal actinomycosis", "pharyngeal actinomycosis", "actinomycosis AND larynx", and "actinomycosis AND pharynx." Articles which did not describe appropriate sites or were non-English were excluded. Results were collected for demographic information, site(s) of infection, comorbidities, lesion characteristics and treatments. RESULTS: Along with three cases reported from our institution, 40 unique cases were reviewed from 37 studies for a total of 43 patients (Table 1). 34 (81.0 %) of the patients were male with the highest incidence of infection in the seventh decade (54.8 %). The most common site for the infection was the larynx (69.0 %) followed by the pharynx (16.7 %). Risk factors included a history of radiation therapy, immunosuppression, inhalational irritant, and diabetes (Table 3). The duration of antibiotic therapy varied greatly, from one month to one year and total follow up ranged from 1 month to 2.5 years (Table 1). CONCLUSIONS: A comprehensive review of the literature on pharyngolaryngeal actinomycosis shows that this infection has increased prevalence within the head and neck cancer patient population. Similar to cervicofacial actinomycosis, these atypical sites have shown favorable responses to extended antibiotic therapy and generally do not require aggressive surgical management.

Deep learning prediction of BRAF-RAS gene expression signature identifies noninvasive follicular thyroid neoplasms with papillary-like nuclear features.

Noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) are follicular-patterned thyroid neoplasms defined by nuclear atypia and indolent behavior. They harbor RAS mutations, rather than BRAFV600E mutations as is observed in papillary thyroid carcinomas with extensive follicular growth. Reliably identifying NIFTPs aids in safe therapy de-escalation, but has proven to be challenging due to interobserver variability and morphologic heterogeneity. The genomic scoring system BRS (BRAF-RAS score) was developed to quantify the extent to which a tumor's expression profile resembles a BRAFV600E or RAS-mutant neoplasm. We proposed that deep learning prediction of BRS could differentiate NIFTP from other follicular-patterned neoplasms. A deep learning model was trained on slides from a dataset of 115 thyroid neoplasms to predict tumor subtype (NIFTP, PTC-EFG, or classic PTC), and was used to generate predictions for 497 thyroid neoplasms within The Cancer Genome Atlas (TCGA). Within follicular-patterned neoplasms, tumors with positive BRS (RAS-like) were 8.5 times as likely to carry an NIFTP prediction than tumors with negative BRS (89.7% vs 10.5%, P < 0.0001). To test the hypothesis that BRS may serve as a surrogate for biological processes that determine tumor subtype, a separate model was trained on TCGA slides to predict BRS as a linear outcome. This model performed well in cross-validation on the training set (R2 = 0.67, dichotomized AUC = 0.94). In our internal cohort, NIFTPs were near universally predicted to have RAS-like BRS; as a sole discriminator of NIFTP status, predicted BRS performed with an AUC of 0.99 globally and 0.97 when restricted to follicular-patterned neoplasms. BRAFV600E-mutant PTC-EFG had BRAFV600E-like predicted BRS (mean -0.49), nonmutant PTC-EFG had more intermediate predicted BRS (mean -0.17), and NIFTP had RAS-like BRS (mean 0.35; P < 0.0001). In summary, histologic features associated with the BRAF-RAS gene expression spectrum are detectable by deep learning and can aid in distinguishing indolent NIFTP from PTCs.

Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies.

BACKGROUND: Lifelong HIV antiretroviral therapy (ART) has prompted an interest in two-drug regimens to minimise cumulative drug exposure and toxicities. The safety, tolerability, and efficacy of dolutegravir and rilpivirine suggest potential compatibility and effectiveness as a two-drug regimen. We aimed to investigate this two-drug regimen in a phase 3 study. METHODS: We identically designed SWORD-1 and SWORD-2, which were open-label, parallel-group, multicentre, phase 3, randomised, non-inferiority studies in 12 countries evaluating efficacy and safety of once-daily dolutegravir 50 mg plus rilpivirine 25 mg versus current ART regimen (CAR). We included participants aged 18 years or older who were on first or second ART with stable plasma HIV-1 RNA (viral load <50 copies per mL) for 6 months or longer at screening. We randomly assigned participants (1:1) with stratification by third-agent class, age, and planned participation in a bone mineral density substudy. The primary endpoint was proportion of participants with viral load lower than 50 copies per mL at week 48 among those individuals who received one or more doses of study medication. Investigators monitored adverse events to assess safety. These trials are registered with ClinicalTrials.gov, numbers NCT02429791 (SWORD-1) and NCT02422797 (SWORD-2). FINDINGS: We screened for participants from April 14, 2015, to Oct 15, 2015, for SWORD-1 and from April 21, 2015, to Sept 25, 2015, for SWORD-2. We randomly assigned 516 participants to dolutegravir-rilpivirine and 512 to continue with CAR. At week 48 (last patient visit was Nov 22, 2016), in the pooled analysis of the intention-to-treat population, 95% of participants had viral loads lower than 50 copies per mL in each group (486 of 513 in the dolutegravir-rilpivirine group vs 485 of 511 in the CAR group), with an adjusted treatment difference of -0·2% (95% CI -3·0 to 2·5) and showed non-inferiority with a predefined margin of -8%. 395 (77%) of 513 participants in the dolutegravir-rilpivirine group and 364 (71%) of 511 participants in the CAR group reported adverse events. The most common adverse events were nasopharyngitis (49 [10%] for dolutegravir-rilpivirine vs 50 [10%] for CAR) and headache (41 [8%] vs 23 [5%]). More participants taking dolutegravir-rilpivirine (17 [3%]) reported adverse events leading to withdrawal than did participants taking CAR (three [<1%]). INTERPRETATION: Dolutegravir-rilpivirine was non-inferior to CAR over 48 weeks in participants with HIV suppression and showed a safety profile consistent with its components. Results support the use of this two-drug regimen to maintain HIV suppression. FUNDING: ViiV Healthcare and Janssen Pharmaceutica NV.

Impact of video technology on efficiency of pharmacist-provided anticoagulation counseling and patient comprehension.

BACKGROUND: Discharge anticoagulation counseling is important for ensuring patient comprehension and optimizing clinical outcomes. As pharmacy resources become increasingly limited, the impact of informational videos on the counseling process becomes more relevant. OBJECTIVE: To evaluate differences in pharmacist time spent counseling and patient comprehension (measured by the Oral Anticoagulation Knowledge [OAK] test) between informational videos and traditional face-to-face (oral) counseling. METHODS: This prospective, open, parallel-group study at an academic medical center randomized 40 individuals-17 warfarin-naïve ("New Start") and 23 with prior warfarin use ("Restart")-to receive warfarin discharge education by video or face-to-face counseling. "Teach-back" questions were used in both groups. RESULTS: Although overall pharmacist time was reduced in the video counseling group (P < 0.001), an interaction between prior warfarin use and counseling method (P = 0.012) suggests the difference between counseling methods was smaller in New Start participants. Following adjustment, mean total time was reduced 8.71 (95% CI = 5.15-12.26) minutes (adjusted P < 0.001) in Restart participants and 2.31 (-2.19 to 6.81) minutes (adjusted P = 0.472) in New Start participants receiving video counseling. Postcounseling OAK test scores did not differ. Age, gender, socioeconomic status, and years of education were not predictive of total time or OAK test score. CONCLUSION: Use of informational videos coupled with teach-back questions significantly reduced pharmacist time spent on anticoagulation counseling without compromising short-term patient comprehension, primarily in patients with prior warfarin use. Study results demonstrate that video technology provides an efficient method of anticoagulation counseling while achieving similar comprehension.

Imaging features and surgical management of giant parathyroid adenoma with autoinfarction.

Autoinfarction of a parathyroid adenoma can have an atypical clinicoradiologic features that can mimic an inflammatory process or malignancy. In addition, the associated fibrosis makes surgical resection more challenging than for regular parathyroid adenomas. The implications of these findings are that while autoinfarction of parathyroid adenomas is a rare phenomenon, this entity should be considered when there are heterogeneous and cystic components on imaging in patients without hypercalcemia. Ultimately, histopathology is necessary for definitive diagnosis.

Neoadjuvant Nivolumab Plus Chemotherapy Followed By Response-Adaptive Therapy for HPV+ Oropharyngeal Cancer: OPTIMA II Phase 2 Open-Label Nonrandomized Clinical Trial.

Importance: Immune checkpoint inhibitors improve survival in recurrent and/or metastatic head and neck cancer, yet their role in curative human papillomavirus-positive oropharyngeal cancer (HPV+ OPC) remains undefined. Neoadjuvant nivolumab and chemotherapy followed by response-adaptive treatment in HPV+ OPC may increase efficacy while reducing toxicity. Objective: To determine the deep response rate and tolerability of the addition of neoadjuvant nivolumab to chemotherapy followed by response-adapted locoregional therapy (LRT) in patients with HPV+ OPC. Design, Setting, and Participants: This phase 2 nonrandomized clinical trial conducted at a single academic center enrolled 77 patients with locoregionally advanced HPV+ OPC from 2017 to 2020. Data analyses were performed from February 10, 2021, to January 9, 2023. Interventions: Addition of nivolumab to neoadjuvant nab-paclitaxel and carboplatin (studied in the first OPTIMA trial) followed by response-adapted LRT in patients with HPV+ OPC stages III to IV. Main Outcomes and Measures: Primary outcome was deep response rate to neoadjuvant nivolumab plus chemotherapy, defined as the proportion of tumors with 50% or greater shrinkage per the Response Evaluation Criteria in Solid Tumors 1.1. Secondary outcomes were progression-free survival (PFS) and overall survival (OS). Swallowing function, quality of life, and tissue- and blood-based biomarkers, including programmed death-ligand 1 (PD-L1) expression and circulating tumor HPV-DNA (ctHPV-DNA), were also evaluated. Results: The 73 eligible patients (median [range] age, 61 [37-82] years; 6 [8.2%] female; 67 [91.8%] male) started neoadjuvant nivolumab and chemotherapy. Deep responses were observed in 51 patients (70.8%; 95% CI, 0.59-0.81). Subsequent risk- and response-adaptive therapy was assigned as follows: group A, single-modality radiotherapy alone or transoral robotic surgery (28 patients); group B, intermediate-dose chemoradiotherapy of 45 to 50 Gray (34 patients); and group C, regular-dose chemoradiotherapy of 70 to 75 Gray (10 patients). Two-year PFS and OS were 90.0% (95% CI, 0.80-0.95) and 91.4% (95% CI, 0.82-0.96), respectively. By response-adapted group, 2-year PFS and OS for group A were 96.4% and 96.4%, and group B, 88.0% and 91.0%, respectively. Lower enteral feeding rates and changes in weight, as well as improved swallowing, were observed among patients who received response-adapted LRT. Pathologic complete response rate among patients who underwent transoral robotic surgery was 67.0%. PD-L1 expression was nonsignificantly higher for deeper responses and improved PFS, and ctHPV-DNA clearance was significantly associated with improved PFS. Conclusions and Relevance: This phase 2 nonrandomized clinical trial found that neoadjuvant nivolumab and chemotherapy followed by response-adapted LRT is feasible and has favorable tolerability, excellent OS, and improved functional outcomes in HPV+ OPC, including among patients with high-risk disease. Moreover, addition of nivolumab may benefit high PD-L1 expressors, and sensitive dynamic biomarkers (eg, ctHPV-DNA) are useful for patient selection. Trial Registration: ClinicalTrials.gov Identifier: NCT03107182.

Practice patterns for initial management of oral leukoplakia amongst otolaryngologists and oral and maxillofacial surgeons.

OBJECTIVE: Oral leukoplakia is encountered frequently by otolaryngologists and oral and maxillofacial surgeons (OMFS). There are no consensus practice management guidelines for oral leukoplakia, resulting in heterogeneity in practice patterns. Characterization of practice patterns of providers who treat oral leukoplakia will be valuable to establish standards of care and future practice guidelines. MATERIAL AND METHODS: A survey was designed by the American Head and Neck Society Cancer Prevention Service collecting demographic and practice management data for treating oral leukoplakia. The survey was approved and distributed to members of the American Academy of Otolaryngology-Head and Neck Surgery and American Association of Oral and Maxillofacial Surgeons. Data analysis was performed using chi square and t-test where appropriate. RESULTS: 396 responses were collected: 83 OMFS, 81 head and neck fellowship-trained providers, and 232 otolaryngologists (non-head and neck fellowship-trained). Providers saw a wide volume of oral leukoplakia (23.0% >30 cases/year, 35.1% 11-30 cases/year, 41.2% 10 or less cases/year), with OMFS seeing more cases of oral leukoplakia. Factors most associated with consideration of initial biopsy included physical exam findings (94.4%), erythroplakia (82.3%), and smoking status (81.6%). The majority of respondents saw patients in follow-up within 1 month (24.8%) or within 1-3 months (46.5%). CONCLUSION: This survey identifies a range of practice patterns in initial management of oral leukoplakia, including indications for biopsy, and time for follow-up. This data provide insight into practice patterns amongst different groups of providers and can potentially lead to consensus guidelines for initial management of oral leukoplakia.

Teachers survive together: Teacher collegial relationships and well-being during the COVID-19 pandemic.

COVID-19 disrupted the ecology of schools and negatively influenced teacher mental health and retention. This mixed-methods study investigates the relationship between teacher well-being and teacher collegial relationships after a year enduring COVID-19 pandemic disruptions. By analyzing data collected through surveys (N = 185) and interviews (N = 27) with U.S. teachers in Spring-Summer 2021, we explore how teacher collegial relationships influenced teacher well-being and unpack how teachers collaborated and supported each other during the pandemic. We find that positive teacher-teacher and teacher-administrator relationships were significantly associated with greater teacher well-being and that teacher-teacher relationships deepened as colleagues engaged in innovative and supportive pedagogical problem solving and provided emotional support, a "silver lining" in education that arose during the pandemic. By sharing and affirming stories of how teachers organized, collaborated, engaged in professional sensemaking, and supported each other's emotional health and resilience, educational leaders can help reaffirm this narrative of teacher collective strength. Moving forward, schools should also create more opportunities for deep teacher collaboration, taking advantage of this opportunity to intentionally build on teachers' growing skills, trust, and capacity to address broad organizational and curricular innovation together. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Regional distribution in female representation in US otolaryngology faculty.

Objectives: To quantify the current proportion of women in otolaryngology at different levels of professorship and determine whether these proportions differ by US region. Methods: Academic rank and gender at all ACGME-accredited otolaryngology programs in the United States were determined from departmental websites, Doximity, and LinkedIn from November 2021 to March 2022. Individuals were then further organized using US Census Bureau-designated regions. Results: Among the 2682 faculty positions at 124 ACGME-accredited programs, women held 706 (26.3%) of these positions. Female representation was highest at the assistant professorship level, with women holding 286 (37.2%) positions out of a total 769. At the associate professorship level, women held 141 (27.6%) of the 511 total positions. The largest gender disparity is seen at the full professorship level; only 69 (13.6%) positions out of 508 were held by women. Out of every region and rank, only assistant professorship in the West had no significant difference in percentages of men and women (p = .710). Female representation of professors in the Northeast was significantly lower than that of our reference group (the South; ß = -10.9, p = .020). Conclusions: Otolaryngology has exhibited great progress in increasing female representation, with assistant professorship in the West reaching gender parity. However, the gender gap at other faculty levels still leaves much to be desired, particularly in senior ranks. The lack of otolaryngologists at senior ranks is detrimental to mentorship of junior faculty, residents, and medical students. Renewed efforts should be made to decrease the gender disparity in the South, Northeast, and particularly at the professorship level.

Advice and perspectives from navigating the couples match in otolaryngology: A qualitative pilot study.

Introduction: There is a lack of qualitative analysis of the personal experiences within Couples Matching. In this qualitative study, we aim to record personal attitudes, reflections, and advice on experiences with the Couples Match process. Methods: Our survey, consisting of two open-ended questions regarding the experience of Couples Matching, was distributed from January 2022 to March 2022 via email to 106 otolaryngology program directors across the nation. Survey responses were analyzed iteratively using the constructivist grounded theory to construct themes related to pre-match priorities, match-related stressors, and post-match satisfaction. Themes were developed inductively and refined iteratively as the dataset evolved. Results: 18 Couples Match residents responded. In response to the first question: "What was the most difficult part of the process for you and/or your partner?", we identified the following themes: cost and financial burden, increased stress on the relationship, sacrificing top choices, and finalizing the match list. In response to the second question: "Using your experience as a previous applicant, what advice would you give to another couple planning on couples matching?", we identified four common themes: compromise, advocacy, dynamic conversations, and applying broadly. Conclusion: We sought to understand the Couples Match process through the perspective of previous applicants. Analyzing the views and attitudes of Couples Match applicants, our study captures the most challenging aspects of the experience and highlights possible areas to improve advising for couples, including important factors to consider when applying, ranking, and interviewing.

Large tracheoesophageal granular cell tumor: An atypical case presentation, location, and management.

INTRODUCTION: Granular cell tumors (GCT) are rare tumors that most frequently present in the oral cavity. While some present within the gastrointestinal tract, a GCT near the trachea is an extremely rare occurence. PRESENTATION OF CASE: A 42-year-old man presented to the Emergency Department after a motor vehicle accident. A computerized tomography (CT) scan revealed an incidental soft tissue 3.2 × 5.5 cm mass anterior to the esophagus and posterior to the trachea with no adjacent lymphadenopathy. The patient denied dyspnea, voice changes, or dysphagia. Due to its size and location, the patient underwent a transcervical excision of the retrotracheal tumor. Tumor cells were positive for CD68, CD163, S100, and SOX10, confirming a GCT. CONCLUSION: This is a distinctive presentation of a large (5 cm) GCT in the plane between the trachea and esophagus. GCTs are not often on the differential diagnosis of masses that present in this region.

Characterizing Lymph Node Burden With Elective Unilateral Neck Irradiation in Human Papillomavirus-Positive Tonsil Squamous Cell Carcinoma: Defining the Upper Limits.

Objectives Elective unilateral neck irradiation in well-lateralized tonsil carcinoma for N2b disease is controversial. Metrics regarding nodal burden beyond the N-stage to define the upper limit of this de-escalation approach remain limited. We investigated the role of nodal number, level, and volume on outcomes in patients with well-lateralized tonsil carcinoma treated with this approach. Methods A total of 37 patients received radiotherapy (RT) with unilateral neck coverage for well-lateralized tonsil cancer. Of patients, 95% had p16+ disease, and 81% were staged with positron emission tomography/computed tomography. The majority of patients received definitive chemoradiation on prospective de-escalation trials. Ten patients had ipsilateral neck dissections and were treated adjuvantly. The median RT dose to the ipsilateral neck (generally II-IV) was 45 Gy. The effects of nodal number, max dimension, volume, and level on recurrence-free survival (RFS) and overall survival (OS) were to be analyzed via Cox proportional hazards (Cox-PH). Results After a median follow-up of 3.9 years, two-year RFS and two-year OS were 100% and 97%, respectively. Given the 0% contralateral recurrence rate, Cox-PH analysis was not performed. Of patients, 70% were American Joint Committee on Cancer (AJCC) 7th edition N2b, with a median number of nodes, number of nodal levels, max dimension, and volume of two, one, 3.4 cm, and 15.6 cc, respectively. There were several patients with low-lying nodes; aggregate nodal volume measured was up to 85.4 cc. Conclusion Unilateral neck irradiation in well-lateralized tonsil carcinoma resulted in no contralateral recurrence. Nodal volume, level, and number do not seem to have a significant impact on outcomes.

Prior chemoradiotherapy adversely impacts outcomes of recurrent and second primary head and neck cancer treated with concurrent chemotherapy and reirradiation.

BACKGROUND: It has been shown that concomitant chemotherapy (C) with reirradiation (ReRT) is feasible and effective for select patients with recurrent or second primary head and neck cancer (HNC). To examine potential prognostic factors associated with survival, the authors of this report retrospectively reviewed the outcomes of patients who received CReRT. METHODS: The study cohort comprised previously irradiated patients with nonmetastatic disease from 9 consecutive phase 1 and 2 protocols for poor-prognosis HNC. For all patients, reirradiation (ReRT) was delivered with concurrent chemotherapy. Chemotherapy generally was 5-fluorouracil, hydroxyurea, and a third agent. RESULTS: One hundred sixty-six patients were identified, including 81 patients who underwent surgical resection or debulking before enrollment. The median ReRT dose was 66 gray. After a median follow-up of 53 months among surviving patients, the median overall survival (OS) was 10.3 months. The 2-year rates for OS, disease-free survival, locoregional control, and freedom from distant metastasis were 24.8%, 19.9%, 50.7%, and 61.4%, respectively. Thirty-three patients (19.9%) died of treatment-related toxicity. In subgroup analysis, survival was significantly reduced in patients who received previous concurrent chemoradiotherapy (CRT) compared with patients who were naive to CRT (2-year OS rate, 10.8% vs 28.4%; P = .0043). In multivariable analysis, prior CRT was associated independently with OS along with surgery before protocol treatment, full-dose ReRT, and radiotherapy interval. CONCLUSIONS: CReRT achieved a long-term cure for a small group of patients with recurrent or second primary HNC. Previous treatment with CRT was among the important prognostic factors for survival. Because of the associated risk of severe toxicity, CReRT should be limited only to carefully selected patients.

Multi-disciplinary management of patients with benign airway strictures: A review.

Histologically benign airway strictures are frequently misdiagnosed as asthma or COPD and may present with severe symptoms including respiratory failure. A clear understanding of pathophysiology and existing classification systems is needed to determine the appropriate treatment options and predict clinical course. Clinically significant airway strictures can involve the upper and central airways extending from the subglottis to the lobar airways. Optimal evaluation includes a proper history and physical examination, neck and chest computed tomography, pulmonary function testing, endoscopy and serology. Available treatments include medical therapy, endoscopic procedures and open surgery which are based on the stricture's extent, location, etiology, morphology, severity of airway narrowing and patient's functional status. The acuity of the process, patient's co-morbidities and operability at the time of evaluation determine the need for open surgical or endoscopic interventions. The optimal management of patients with benign airway strictures requires the availability, expertise and collaboration of otolaryngologists, thoracic surgeons and interventional pulmonologists. Multidisciplinary airway teams can facilitate accurate diagnosis, guide management and avoid unnecessary procedures that could potentially worsen the extent of the disease or clinical course. Implementation of a complex airway program including multidisciplinary clinics and conferences ensures that such collaboration leads to timely, patient-centered and evidence-based interventions. In this article we outline algorithms of care and illustrate therapeutic techniques based on published evidence.

Associations of school night sleep duration and circadian preference with middle school-aged student attendance, tardiness, and suspension.

OBJECTIVES: Research has associated both school night sleep duration (SNSD) and circadian preference (CP) with middle school-aged students' attendance and tardiness, but the interaction between these characteristics remains unexplored within this context, along with the impact of SNSD and CP on school suspension likelihood. Thus, this study investigated associations between SNSD, CP, and their interaction with middle school-aged student attendance, tardiness, and suspension, while accounting for sociodemographic characteristics. PARTICIPANTS: About 4175 students from 12 middle schools in the Madison, Wisconsin, Metropolitan School District. METHODS: Students completed a computer-based, sleep-related survey during class. Students reporting SNSD between 4 and 12 hours were included in the final analytical sample (N = 3860; mean age ± standard deviation = 12.0 ± 0.86 years; range = 10-16 years). CP was characterized using the single-item self-morningness/eveningness question. Linear mixed-effects regression estimated associations of SNSD and CP with tardiness and attendance. Logistic mixed-effects regression assessed associations with school suspension. Fully adjusted multilevel models included sociodemographic covariates, nesting students within schools. RESULTS: About 3860 student responses comprised the final sample, which had a SNSD of 8.15 ± 1.37 hours and general eveningness preference. Short-and-long SNSD associated with lower attendance and increased out-of-school suspension. Greater eveningness preference was negatively associated with attendance and tardiness. No SNSD and CP interactions emerged. Associations between sociodemographic characteristics and attendance, tardiness, and suspension were observed. CONCLUSIONS: Results support need for efforts to improve middle school-aged student sleep health and account for eveningness preference. Research clarifying the interactive influence of sleep, circadian, and sociodemographic characteristics on attendance and achievement is warranted.

Risk and response adapted de-intensified treatment for HPV-associated oropharyngeal cancer: Optima paradigm expanded experience.

BACKGROUND: Favorable prognosis for Human papillomavirus-associated (HPV+) oropharyngeal cancer (OPC) led to investigation of response-adaptive de-escalation, yet long-term outcomes are unknown. We present expanded experience and follow-up of risk/response adaptive treatment de-intensification in HPV+ OPC. METHODS: A phase 2 trial (OPTIMA) and subsequent cohort of sequential off-protocol patients treated from September 2014 to November 2018 at the University of Chicago were reviewed. Eligible patients had T3-T4 or N2-3 (AJCC 7th edition) HPV+ OPC. Patients were stratified by risk: High-risk (HR) (T4, ≥N2c, or >10PYH), all others low-risk (LR). Induction chemotherapy (IC) included 3 cycles of carboplatin and nab-paclitaxel (OPTIMA) or paclitaxel (off-protocol). LR with ≥50% response received low-dose radiotherapy (RT) alone to 50 Gy (RT50). LR with 30-50% response and HR with ≥50% response received intermediate-dose chemoradiotherapy (CRT) to 45 Gy (CRT45). All others received full-dose CRT to 75 Gy (CRT75). RESULTS: 91 patients consented and 90 patients were treated, of which 31% had >10PYH, 34% had T3/4 disease, and 94% had N2b/N2c/N3 disease. 49% were LR and 51% were HR. Overall response rate to induction was 88%. De-escalated treatment was administered to 83%. Median follow-up was 4.2 years. Five-year OS, PFS, LRC, and DC were 90% (95% CI 81,95), 90% (95% CI 80,95), 96% (95% CI 90,99), and 96% (88,99) respectively. G-tube placement rates in RT50, CRT45, and CRT75 were 3%, 33%, and 80% respectively (p < 0.05). CONCLUSION: Risk/response adaptive de-escalated treatment for an inclusive cohort of HPV+ OPC demonstrates excellent survival with reduced toxicity with long-term follow-up.