Faculty Bibliography

PURPOSE/OBJECTIVE:A multicenter, randomized study was undertaken to estimate the single agent activity of Tositumomab and to determine the contribution of radioisotope-labeling with (131)I to activity and toxicity by comparing treatment outcomes for Tositumomab and Iodine I 131 Tositumomab (BEXXAR) to an equivalent total dose of unlabeled Tositumomab. EXPERIMENTAL DESIGN/METHODS:Seventy-eight patients with refractory/relapsed non-Hodgkin's lymphoma were randomized to either unlabeled Tositumomab or Iodine I 131 Tositumomab. Patients progressing after unlabeled Tositumomab could cross over to receive Iodine I 131 Tositumomab. The median follow-up at analysis was 42.6 months (range 1.9 to 71.5 months). RESULTS:Responses in the Iodine I 131 Tositumomab versus unlabeled Tositumomab groups: overall response 55% versus 19% (P = 0.002); complete response 33% versus 8% (P = 0.012); median duration of overall response not reached versus 28.1 months (95% confidence interval: 7.6, not reached); median duration of complete response not reached in either arm; and median TTP 6.3 versus 5.5 months (P = 0.031), respectively. Of the patients who had a complete response after initial Iodine I 131 Tositumomab therapy, 71% (10 of 14) continued in complete response at 29.8 to 71.1 months. Two patients who achieved a complete response after unlabeled Tositumomab had ongoing responses at 48.1 to 56.9 months. Nineteen patients received Iodine I 131 Tositumomab crossover therapy. Responses after crossover versus prior response to unlabeled Tositumomab were as follows: complete response rates of 42% versus 0% (P = 0.008); overall response 68% versus 16% (P = 0.002); median durations of overall response 12.6 versus 7.6 months (P = 0.001); and median TTP 12.4 versus 5.5 months (P = 0.01), respectively. Hematologic toxicity was more severe and nonhematologic adverse events were more frequent after Iodine I 131 Tositumomab than after Tositumomab alone. Elevated thyrotropin occurred in 5% of patients. Seroconversion to human antimurine antibody after Iodine I 131 Tositumomab, unlabeled Tositumomab, and Iodine I 131 Tositumomab-crossover was 27%, 19%, and 0%, respectively. CONCLUSIONS:Unlabeled Tositumomab showed single agent activity, but in this direct comparison, all of the therapeutic outcome measures were significantly enhanced by the conjugation of (131)I to Tositumomab.

OBJECTIVE/HYPOTHESIS/OBJECTIVE:The utility of elective neck dissection in the management of patients with oral cavity and oropharyngeal cancer who present without neck metastases remains controversial. The study addressed the question of whether elective neck dissection improves regional control and survival in patients with squamous cell carcinoma of the oral cavity and oropharynx presenting with T1/T2 node-negative disease. STUDY DESIGN/METHODS:A nonrandomized, uncontrolled retrospective chart review. METHODS:A nonrandomized, uncontrolled retrospective chart review was performed. Resection of the primary tumor was performed in all patients. The neck was observed in one group, and elective neck dissection was performed for patients in another group. RESULTS:The study data indicated that elective neck dissection significantly improves regional control and regional recurrence-free survival. Elective neck dissection when compared with observation of the neck did not improve overall survival. CONCLUSION/CONCLUSIONS:Elective neck dissection reduces regional recurrence and may extend disease-free survival.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:To assess factors that may be predictive of patient perception of dysphonia severity, as quantified by the Voice Handicap Index (VHI) score. We hypothesize that 1) level of vocal demand; 2) auditory-perceptual evaluation of dysphonia severity; and 3) vocal function, as defined by phonatory glottal closure and mucosal wave vibration, are the most significant predictors of VHI score. STUDY DESIGN/METHODS:: Retrospective review of 100 patients with benign vocal fold lesions. METHODS:Variables assessed for predictive value to VHI score are level of vocal demands, auditory-perceptual evaluation of dysphonia severity, integrity of mucosal wave vibration and phonatory glottal closure, lesion type, duration of current complaint, smoking, age, and sex. Harmonic to noise ratio was assessed in a subset of 50 patients. RESULTS:Patients with routine voice use had significantly lower VHI scores than those with more intensive (nonsinging/acting) vocal demands. Patients who quit smoking had greater VHI scores than those who currently smoke or never started. Patients with long-standing dysphonia tended to have lower VHI scores than those with shorter duration vocal complaints. Auditory-perceptual assessment of dysphonia severity and harmonic to noise ratio were weak predictors of VHI score. Age, sex, lesion type, phonatory glottal closure, and mucosal wave vibration were not significant predictors of VHI score. CONCLUSIONS:Patient perception of dysphonia severity is independent of many factors commonly assessed during the evaluation of voice disorders. It appears to be an important independent element in the assessment of the effect of a benign vocal fold lesion and critical to therapeutic decision-making.

OBJECTIVES/OBJECTIVE:Placebo response is defined as a change in health status resulting from the symbolic significance attributed by the patient or proxy to the physician encounter. Our goals were to validate the PR12 survey as a measure of placebo response and to analyze the placebo response as a discrete and measurable component of everyday office encounters with the otolaryngologist. STUDY DESIGN/METHODS:This was a prospective, before-and-after clinical outcomes study of 95 children aged 6 months to 12 years conducted in an academic metropolitan pediatric otolaryngology practice. Caregivers completed the PR-12 survey at entry and at least 4 weeks later. The survey included 3 domains (4 questions each) reflecting the main components of the placebo response: meaningful explanation, care and concern, and mastery and control. PR-12 was correlated with longitudinal change in health status at least 1 to 2 months after the baseline visit. Outcome measures included direct and indirect measures of change in disease-specific quality of life and satisfaction with change. RESULTS:Test-retest reliability was fair for most PR-12 survey items (R = 0.41 to 0.76) but was higher for domains (0.60 to 0.66) and the overall survey score (0.66). PR-12 had excellent internal consistency (Cronbach's alpha 0.91) and appropriate construct validity. Caregiver satisfaction change at follow-up correlated with the PR-12 (r = -.25, P = 0.036). Conversely, no correlation was seen between the PR-12 and direct and indirect measures of change in disease specific quality of life. CONCLUSION/CONCLUSIONS:Placebo response is an important and potentially measurable aspect of clinical encounters. PR-12 is a promising first step at creating a brief, reliable, and valid instrument to assess the placebo response. SIGNIFICANCE/CONCLUSIONS:Reemphasizing the therapeutic potential of the doctor-patient relationship may improve quality of care and disease outcomes.

Childhood-onset dystonia is an autosomal dominant movement disorder associated with a three base pair (GAG) deletion mutation in the DYT1 gene. This gene encodes a novel ATP-binding protein called torsinA, which in the central nervous system is expressed exclusively in neurons. Neither the function of torsinA nor its role in the pathophysiology of DYT1 dystonia is known. In order to better understand the cellular functions of torsinA, we established PC12 cell lines overexpressing wild-type or mutant torsinA and subjected them to various conditions deleterious to cell survival. Treatment of control PC12 cells with an inhibitor of proteasomal activity, an oxidizing agent, or trophic withdrawal, resulted in cell death, whereas PC12 cells that overexpressed torsinA were significantly protected against each of these treatments. Overexpression of mutant torsinA failed to protect cells against trophic withdrawal. These results suggest that torsinA may play a protective role in neurons against a variety of cellular insults.

OBJECTIVE: To better define the clinical manifestations, radiologic imaging and the surgical management of cervical thymic lesions in children. STUDY DESIGN: Multi-center retrospective case review. METHODS: The charts of all children with pathologically confirmed thymic lesions at six children's hospitals (1990-2002) were reviewed for demographics, physical findings, X-ray findings, operative outcomes and pathology. RESULTS: There were a total of 15 children, 2 of whom had ectopic cervical thymus and 13 who had thymic cysts. They ranged in age from 1 month to 18 years. Thymic lesions were more common in males. Ectopic cervical thymus was best defined by MRI whereas thymic cyst had a more consistent appearance on CT. All children had successful surgical resection with no recorded complications or recurrences. CONCLUSIONS: Cervical thymic lesions are rare. Ectopic cervical thymus tends to be found primarily in infants whereas thymic cysts occur in a wider age range. Radiologic imaging is important but is not histologically specific. Definitive diagnosis and cure requires complete surgical excision.