Brian Nussenbaum

A PRACTICAL GUIDE TO UNDERSTANDING KAPLAN-MEIER CURVES

In 1958, Edward L. Kaplan and Paul Meier collaborated to publish a seminal paper on how to deal with incomplete observations. Subsequently, the Kaplan-Meier curves and estimates of survival data have become a familiar way of dealing with differing survival times (times-to-event), especially when not all the subjects continue in the study. “Survival” times need not relate to actual survival with death being the event; the “event” may be any event of interest. Kaplan-Meier analyses are also used in nonmedical disciplines. The purpose of this article is to explain how Kaplan-Meier curves are generated and analyzed. Throughout this article, we will discuss Kaplan-Meier estimates in the context of “survival” before the event of interest. Two small groups of hypothetical data are used as examples in order for the reader to clearly see how the process works. These examples also illustrate the crucially important point that comparative analysis depends upon the whole curve and not upon isolated points.

Paranasal sinus malignancies: An 18-year single institution experience

Objectives To characterize a single institution experience with management of paranasal sinus malignancies during an 18‐year time period, report long‐term survival rates, and identify prognostic factors.

Clinical consensus statement: tracheostomy care.

Objective This clinical consensus statement (CCS) aims to improve care for pediatric and adult patients with a tracheostomy tube. Approaches to tracheostomy care are currently inconsistent among clinicians and between different institutions. The goal is to reduce variations in practice when managing patients with a tracheostomy to minimize complications. Methods A formal literature search was conducted to identify evidence gaps and refine the scope of this consensus statement. The modified Delphi method was used to refine expert opinion and facilitate a consensus position. Panel members were asked to complete 2 scale-based surveys addressing different aspects of pediatric and adult tracheostomy care. Each survey was followed by a conference call during which results were presented and statements discussed. Results The panel achieved consensus on 77 statements; another 39 were dropped because of lack of consensus. Consensus was reached on statements that address initial tracheostomy tube change, management of emergencies and complications, prerequisites for decannulation, management of tube cuffs and communication devices, and specific patient and caregiver education needs. Conclusion The consensus panel agreed on statements that address the continuum of care, from initial tube management to complications in children and adults with a tracheostomy. The panel also highlighted areas where consensus could not be reached and where more research is needed. This consensus statement should be used by physicians, nurses, and other stakeholders caring for patients with a tracheostomy.

Systematic management of chyle fistula: The Southwestern experience and review of the literature:

Postoperative cervical chyle fistula after neck dissection is a complication with potentially serious morbidity. Once it is recognized, treatment decisions to optimize patient care can be difficult. Different management strategies have been advocated on the basis of institutional and personal experience. In this study we comprehensively review the published protocols and retrospectively review our experience in the management of 15 patients with chyle fistula. All patients in this study were given a trial of nonoperative management with nutritional modification, pressure dressings, and closed drainage. Medical management ultimately failed in 3 patients (20%). Two patients had prolonged courses of medical management with associated complications. An analysis of our data supports early operative intervention if the peak 24hour drainage is greater than 1000 mL without a prompt response to medical management. Persistent low-output drainage after 10 days is associated with a prolonged management course and treatment-related complications. Optimal treatment of these patients is unclear. (Otolaryngol Head Neck Surg 2000;122:31–8.)

Characteristics of Bony Erosion in Allergic Fungal Rhinosinusitis

OBJECTIVES: Erosion of bone with or without extension of disease into adjacent anatomic spaces is observed among some patients with allergic fungal rhinosinusitis (AFRS). The objective of this report is to further define these findings as they relate to this disease. STUDY DESIGN: Retrospective chart review of 142 patients with AFRS diagnosed using the Bent-Kuhn criteria. All patients were treated at a single institution. RESULTS: Approximately 20% of patients with AFRS demonstrated bone erosion on CT scan. The ethmoid sinus was the most commonly eroded site. The orbit and anterior cranial fossa were the most common adjacent anatomic spaces to exhibit disease extension. Sinus expansion, not the specific organism identified, was associated with the presence of bone erosion. Surgical management with endoscopic techniques was successful for all patients without any major perioperative complications. CONCLUSION: Bone erosion can be related to AFR. Recognition of this possibility is important because bone erosion can be interpreted as an indication of invasive pathosis. In the presence of bone erosion or disease extension, endoscopic techniques can be used to surgically manage this disease.

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.

Clinical Presentation of Allergic Fungal Sinusitis in Children

Objective To compare the differences in the clinical and radiographic presentation of allergic fungal sinusitis in children and adults.

Ex Vivo Gene Therapy for Skeletal Regeneration in Cranial Defects Compromised by Postoperative Radiotherapy

Because radiation remains a common postoperative treatment for head and neck cancers, it is critical to determine whether new bone-regenerative approaches are effective for healing craniofacial defects challenged by therapeutic doses of radiation. The objective of this study was to determine whether the deleterious effects of radiotherapy could be overcome by ex vivo gene therapy to heal craniofacial defects. Rat calvarial critical-sized defects were treated with either an inlay calvarial bone graft or syngeneic dermal fibroblasts transduced ex vivo with an adenovirus engineered to express bone morphogenetic protein 7 (BMP-7), a morphogen known to stimulate bone formation. Two weeks postoperatively, either no radiation or a single 12-Gy radiation dose was delivered to the operated area and the tissue was harvested 4 weeks later. None of the inlay bone grafts healed at the wound margins of either the radiated or nonradiated sites. In contrast, bone was successfully regenerated when using an ex vivo gene therapy approach. More bone formed in the nonradiated group as determined by the percentage of defect surface covered (87 +/- 4.1 versus 65 +/- 4.7%; p = 0.003) and percentage of defect area filled by new bone (60 +/- 5.9 versus 32 +/- 2.7%; p = 0.002). Although the effects of radiation on the wound were not completely overcome by the gene therapy approach, bone regeneration was still successful despite the radiation sensitivity of the fibroblasts. These results indicate that BMP-7 ex vivo gene therapy is capable of successfully regenerating bone in rat calvarial defects even after a therapeutic dose of radiation. This approach may represent a new strategy for regenerating skeletal elements lost due to head and neck cancer.

Assessment of Cellular Proliferation in Tumors by PET Using 18F-ISO-1

This first study in humans was designed to evaluate the safety and dosimetry of a cellular proliferative marker, N-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-18F-fluoroethoxy)-5-methylbenzamide (18F-ISO-1), and evaluate the feasibility of imaging tumor proliferation by PET in patients with newly diagnosed malignant neoplasms. Methods: Patients with biopsy-proven lymphoma, breast cancer, or head and neck cancer underwent 18F-ISO-1 PET. Tumor 18F-ISO-1 uptake was assessed semiquantitatively by maximum standardized uptake value, ratios of tumor to normal tissue and tumor to muscle, and relative distribution volume ratio. The PET results were correlated with tumor Ki-67 and mitotic index, from in vitro assays of the tumor tissue. The biodistribution of 18F-ISO-1 and human dosimetry were evaluated. Results: Thirty patients with primary breast cancer (n = 13), head and neck cancer (n = 10), and lymphoma (n = 7) were evaluated. In the entire group, tumor maximum standardized uptake value and tumor-to-muscle ratio correlated significantly with Ki-67 (τ = 0.27, P = 0.04, and τ = 0.38, P = 0.003, respectively), but no significant correlation was observed between Ki-67 and tumor–to–normal-tissue ratio (τ = 0.07, P = 0.56) or distribution volume ratio (τ = 0.26, P = 0.14). On the basis of whole-body PET data, the gallbladder is the dose-limiting organ, with an average radiation dose of 0.091 mGy/MBq. The whole-body and effective doses were 0.012 mGy/MBq and 0.016 mSv/MBq, respectively. No adverse effects of 18F-ISO-1 were encountered. Conclusion: The presence of a significant correlation between 18F-ISO-1 and Ki-67 makes this agent promising for evaluation of the proliferative status of solid tumors. The relatively small absorbed doses to normal organs allow for the safe administration of up to 550 MBq, which is sufficient for PET imaging in clinical trials.