Dorina Kallogjeri

Extracapsular spread and adjuvant therapy in human papillomavirus‐related, p16‐positive oropharyngeal carcinoma

Extracapsular spread (ECS) is commonly used to justify adjuvant chemotherapy in patients with head and neck cancer. The role of ECS as a prognosticator and adjuvant therapy determinant in surgically resected, human papillomavirus‐related oropharyngeal squamous cell carcinoma (OPSCC), however, has never been determined.

Survival among men with clinically localized prostate cancer treated with radical prostatectomy or radiation therapy in the prostate specific antigen era

PURPOSE Radical prostatectomy, external beam radiotherapy and brachytherapy are accepted treatments for localized prostate cancer. However, it is unknown if survival differences exist among treatments. We analyzed the survival of patients treated with these modalities according to contemporary standards. MATERIALS AND METHODS A total of 10,429 consecutive patients with localized prostate cancer treated with radical prostatectomy (6,485), external beam radiotherapy (2,264) or brachytherapy (1,680) were identified. Multivariable regression analyses were used to model the disease (biopsy grade, clinical stage, prostate specific antigen) and patient specific (age, ethnicity, comorbidity) parameters for overall survival and prostate cancer specific mortality. Propensity score analysis was used to adjust for differences in observed background characteristics. RESULTS The adjusted 10-year overall survival after radical prostatectomy, external beam radiotherapy and brachytherapy was 88.9%, 82.6% and 81.7%, respectively. Adjusted 10-year prostate cancer specific mortality was 1.8%, 2.9% and 2.3%, respectively. Using propensity score analysis, external beam radiotherapy was associated with decreased overall survival (HR 1.6, 95% CI 1.4-1.9, p<0.001) and increased prostate cancer specific mortality (HR 1.5, 95% CI 1.0-2.3, p=0.041) compared to radical prostatectomy. Brachytherapy was associated with decreased overall survival (HR 1.7, 95% CI 1.4-2.1, p<0.001) but not prostate cancer specific mortality (HR 1.3, 95% CI 0.7-2.4, p=0.5) compared to radical prostatectomy. CONCLUSIONS After adjusting for major confounders, radical prostatectomy was associated with a small but statistically significant improvement in overall and cancer specific survival. These survival differences may arise from an imbalance of confounders, differences in treatment related mortality and/or improved cancer control when radical prostatectomy is performed as initial therapy.

Medialization versus reinnervation for unilateral vocal fold paralysis: a multicenter randomized clinical trial.

Vocal fold medialization laryngoplasty (ML) and laryngeal reinnervation (LR) as treatments for unilateral vocal fold paralysis (UVFP) were compared in a multicenter, prospective, randomized clinical trial.

Complications of Primary and Revision Functional Endoscopic Sinus Surgery for Chronic Rhinosinusitis

The goal of this study was to determine the incidence of major complications following primary and revision functional endoscopic sinus surgery (FESS). In addition, this study aimed to determine factors associated with the occurrence of complications including patient and provider characteristics and the use of image guidance system (IGS) technology.

High metastatic node number, not extracapsular spread or N-classification is a node-related prognosticator in transorally-resected, neck-dissected p16-positive oropharynx cancer

BACKGROUND Due to unique biology and prognosis, precise identification of predictive parameters is critical for p16+ oropharyngeal squamous cell carcinoma (OPSCC). Prior studies showing absence of prognostication from extracapsular spread (ECS) and/or high N-classification in surgically-treated p16+ OPSCC necessitate new, evidence-based prognosticators. METHODS A prospectively assembled cohort of 220, transoral surgery+neck dissection±adjuvant therapy-treated, p16+ OPSCC patients was analyzed. Disease recurrence and disease-specific survival (DSS) were primary endpoints. RESULTS Median follow-up was 59 (12-189) months. Distribution of metastatic node numbers was: 0 in 9.5% (n=21), 1 in 33.6% (n=74), 2 in 17% (n=38), 3 in 14.5% (n=32), 4 in 8.2% (n=18), and ⩾5 in 17% (n=37). ECS was recorded in 80% (n=159), and N2c-N3 in 17% (n=38). Adjuvant radiotherapy and chemoradiotherapy was administered in 44% and 34%. Recurrence developed in 22 patients (10%); 4 local, 5 regional, 2 regional and distant, and 11 distant. The 3- and 5-year DSS estimates were 94.6% and 93%. Multivariable logistic regression identified ⩾5 nodes and T3-T4 classification as predictors for recurrence. In multivariable Cox analyses, ⩾5 nodes, T3-T4 classification and margins were prognostic for DSS. ECS, N2c-N3 classification and smoking were not prognostic. CONCLUSIONS Metastatic node number, not ECS or high N-classification is an independent nodal predictor of outcomes in surgically-treated p16+ OPSCC patients. Despite high DSS (~80%), closer surveillance for recurrence is recommended for patients with ⩾5 metastatic nodes.

Risk Factors for Unplanned Hospital Readmission in Otolaryngology Patients

Objective Identify the risk factors that predict 30-day unplanned readmission in hospitalized otolaryngology patients. Study Design Retrospective cohort study. Setting Single academic hospital. Subjects and Methods All otolaryngology admissions for the 1-year period between January 1, 2011, and December 31, 2011, at an academic hospital were reviewed. Univariate logistic regression and multivariate logistic regression, employing a backward elimination stepwise approach, were performed to identify risk factors for unplanned readmission to the hospital within 30 days of discharge from the otolaryngology service. Results There were 1058 patients that accounted for 1271 hospital admissions. The 30-day unplanned readmission rate for patients discharged from the otolaryngology service was 7.3% (93/1271). Significant predictors identified on univariate analysis were used to build a multivariable logistic regression model of risk factors for unplanned readmission. These risk factors included presence of a complication (odds ratio [OR] = 11.60, 95% confidence interval [CI], 7.11-18.93), new total laryngectomy (OR = 4.72, 95% CI, 1.58-14.10), discharge destination of skilled nursing facility (OR = 2.70, 95% CI, 1.21-6.02), severe coronary artery disease or chronic lung disease (OR = 2.33, 95% CI, 1.38-3.93), and current illicit drug use (OR = 2.60, 95% CI, 1.27-5.34). The discriminative ability of the multivariate regression model to predict unplanned readmissions, as measured by the c-statistic, was 0.85. Conclusion Otolaryngology patients have unique risk factors that predict unplanned readmission within 30 days of discharge. These data identify specific patient characteristics and care processes that can be targeted with quality improvement interventions to decrease unplanned readmissions.

Mortality After Prostate Cancer Treatment with Radical Prostatectomy, External-Beam Radiation Therapy, or Brachytherapy in Men Without Comorbidity

BACKGROUND Medical comorbidity is a confounding factor in prostate cancer (PCa) treatment selection and mortality. Large-scale comparative evaluation of PCa mortality (PCM) and overall mortality (OM) restricted to men without comorbidity at the time of treatment has not been performed. OBJECTIVE To evaluate PCM and OM in men with no recorded comorbidity treated with radical prostatectomy (RP), external-beam radiation therapy (EBRT), or brachytherapy (BT). DESIGN, SETTING, AND PARTICIPANTS Data from 10 361 men with localized PCa treated from 1995 to 2007 at two academic centers in the United States were prospectively obtained at diagnosis and retrospectively reviewed. We identified 6692 men with no recorded comorbidity on a validated comorbidity index. Median follow-up after treatment was 7.2 yr. INTERVENTION Treatment with RP in 4459 men, EBRT in 1261 men, or BT in 972 men. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Univariate and multivariate Cox proportional hazards regression analysis, including propensity score adjustment, compared PCM and OM for EBRT and BT relative to RP as reference treatment category. PCM was also evaluated by competing risks analysis. RESULTS AND LIMITATIONS Using Cox analysis, EBRT was associated with an increase in PCM compared with RP (hazard ratio [HR]: 1.66; 95% confidence interval [CI], 1.05-2.63), while there was no statistically significant increase with BT (HR: 1.83; 95% CI, 0.88-3.82). Using competing risks analysis, the benefit of RP remained but was no longer statistically significant for EBRT (HR: 1.55; 95% CI, 0.92-2.60) or BT (HR: 1.66; 95% CI, 0.79-3.46). In comparison with RP, both EBRT (HR: 1.71; 95% CI, 1.40-2.08) and BT (HR: 1.78; 95% CI, 1.37-2.31) were associated with increased OM. CONCLUSIONS In a large multicenter series of men without recorded comorbidity, both forms of radiation therapy were associated with an increase in OM compared with surgery, but there were no differences in PCM when evaluated by competing risks analysis. These findings may result from an imbalance of confounders or differences in mortality related to primary or salvage therapy.

A surprising cross-species conservation in the genomic landscape of mouse and human oral cancer identifies a transcriptional signature predicting metastatic disease

Purpose: Improved understanding of the molecular basis underlying oral squamous cell carcinoma (OSCC) aggressive growth has significant clinical implications. Herein, cross-species genomic comparison of carcinogen-induced murine and human OSCCs with indolent or metastatic growth yielded results with surprising translational relevance. Experimental Design: Murine OSCC cell lines were subjected to next-generation sequencing (NGS) to define their mutational landscape, to define novel candidate cancer genes, and to assess for parallels with known drivers in human OSCC. Expression arrays identified a mouse metastasis signature, and we assessed its representation in four independent human datasets comprising 324 patients using weighted voting and gene set enrichment analysis. Kaplan–Meier analysis and multivariate Cox proportional hazards modeling were used to stratify outcomes. A quantitative real-time PCR assay based on the mouse signature coupled to a machine-learning algorithm was developed and used to stratify an independent set of 31 patients with respect to metastatic lymphadenopathy. Results: NGS revealed conservation of human driver pathway mutations in mouse OSCC, including in Trp53, mitogen-activated protein kinase, phosphoinositide 3-kinase, NOTCH, JAK/STAT, and Fat1-4. Moreover, comparative analysis between The Cancer Genome Atlas and mouse samples defined AKAP9, MED12L, and MYH6 as novel putative cancer genes. Expression analysis identified a transcriptional signature predicting aggressiveness and clinical outcomes, which were validated in four independent human OSCC datasets. Finally, we harnessed the translational potential of this signature by creating a clinically feasible assay that stratified patients with OSCC with a 93.5% accuracy. Conclusions: These data demonstrate surprising cross-species genomic conservation that has translational relevance for human oral squamous cell cancer. Clin Cancer Res; 20(11); 2873–84. ©2014 AACR.

Distant metastasis in p16-positive oropharyngeal squamous cell carcinoma: a critical analysis of patterns and outcomes.

OBJECTIVE With good loco-regional control, disease failure in p16-positive oropharyngeal squamous cell carcinoma (OPSCC) mainly results from distant metastasis (DM). Our objective was to characterize the patterns and clinical outcomes of DM in p16-positive OPSCC and compare these to patients with p16-negative disease. METHODS Primary OPSCC patients who developed DM after completing surgical or non-surgical treatment were identified and p16 status was evaluated. Patterns of DM and post-DM progression-free (PFS) and disease-specific survival (DSS) were assessed. RESULTS Forty-one of the 66 (62%) patients with DM were p16-positive. DM patterns were not statistically different by p16 status. However, p16-positive patients developed DM later in their course and had longer survival. All p16-negative patients either had progression or died within 24 months of DM detection whereas the 2-year post-DM PFS in the p16-positive group was 20% (95% CI: 8-32.5%, p=0.003). The 3-year post-DM disease-specific survival (DSS) estimate in the p16-positive patients was 16% (95% CI: 7-18%) while all p16-negative patients died within 34 months (p<0.001). p16-negativity, loco-regional disease, and no/palliative versus curative intent treatment were all associated with reduced post-DM DSS in multivariate analysis. CONCLUSIONS The DM pattern did not differ remarkably between p16-positive and negative OPSCC patients in our practice. In p16-positive OPSCC with pulmonary oligometastatic disease, curative intent treatment and optimized locoregional control for the index primary prolonged survival.

Patients Undergoing Total Laryngectomy: An At-Risk Population for 30-Day Unplanned Readmission

IMPORTANCE Patients undergoing total laryngectomy are at high risk for hospital readmission. Hospital readmissions are increasingly scrutinized because they are used as a metric of quality care and are subject to financial penalties. OBJECTIVE To determine the rate of, reasons for, and risk factors that predict 30-day unplanned readmission for patients undergoing total laryngectomy. DESIGN, SETTING, AND PATIENTS Retrospective cohort study at a single academic tertiary referral medical center. The study population comprised 155 patients who underwent total laryngectomy with or without flap closure between January 2007 and December 2012 as either a primary treatment or salvage treatment for prior nonsurgical management. INTERVENTIONS Total laryngectomy. MAIN OUTCOMES AND MEASURES Rate of 30-day unplanned readmission, readmission diagnoses, and risk factors for unplanned readmission. Univariable and multivariable logistic regression were performed to identify risk factors for unplanned readmission within 30 days of discharge. RESULTS The 30-day unplanned readmission rate for patients following discharge after total laryngectomy was 26.5% (41 of 155). The most common readmission diagnoses were pharyngocutaneous fistula (27% of readmissions; n = 11) and stomal cellulitis (16% of readmissions; n = 7). The median time to unplanned readmission was 7 days. Thirty-four percent of readmissions (14 of 41) occurred within 3 days of discharge. Significant predictors of 30-day unplanned readmission on multivariable analysis were postoperative complication after discharge (odds ratio [OR], 11.50; 95% CI, 4.10-32.28), visit to the emergency department within 30 days after discharge (OR, 5.25; 95% CI, 1.84-14.99), salvage total laryngectomy (OR, 3.52; 95% CI, 1.56-13.12), and chyle fistula during the index hospitalization (OR, 5.25; 95% CI, 0.86-29.92). The discriminative ability of the model to predict unplanned readmission, as measured by the C statistic, was 0.88. CONCLUSIONS AND RELEVANCE Patients undergoing total laryngectomy are an at-risk patient population with a high rate of unplanned readmission within 30 days of discharge. By identifying the risk factors that predict 30-day unplanned readmission, these data can be used to design and implement quality-improvement interventions to decrease readmissions.