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Literature Review: A Roundup of Important Recent Studies

TORS Alone Effective for Select Cases of Oropharyngeal Cancer

Is transoral robotic surgery (TORS) adequate treatment for oropharyngeal squamous cell cancer (OPSCC)?

Background: OPSCC is increasingly treated non-surgically with radiation therapy or chemoradiation, due to morbidity of primary site resection and a high incidence of nodal metastases. TORS has been proposed as an alternative approach to surgical resection because it is associated with lower morbidity than transmandibular or transcervical approaches. It is unclear whether TORS with staged neck dissection is adequate treatment in patients without high-risk pathologic features.

Study design: Retrospective review.

Setting: University of Pennsylvania Medical Center tertiary care hospital.

Synopsis: Thirty previously untreated patients with OPSCC underwent TORS for primary site resection followed by staged neck dissection. Human papilloma virus (HPV) status was not reported for this cohort. The majority of patients had T1 (30 percent) or T2 (53 percent) tumors and N0 (50 percent) or N1 (33 percent) nodal stage. Patients with N2c and N3 disease and those with extracapsular spread on pathologic analysis of nodal specimens were excluded from analysis. The mean follow-up was 18 months. One patient had a positive margin successfully treated with re-resection. Ten cases had pathologic nodal disease; the number of lymph nodes involved was not reported. Two patients had perineural invasion on histopathology. One patient with a T2 initial lesion developed local recurrence less than four months after TORS and was treated with chemoradiation. Three patients developed regional recurrence, two of whom presented with N2b disease and one with initial N0 disease. Two recurrences occurred in the ipsilateral dissected neck and one in the contralateral neck, and all were subsequently treated with chemoradiation. The overall survival rate was 100 percent. At last follow-up, no patient required a feeding tube.

Bottom line: TORS combined with neck dissection may be adequate treatment for a select group of OPSCC patients with limited primary site and nodal disease when clear margins can be accomplished and extracapsular spread is not present in lymph nodes. A limitation of this study is lack of information regarding the number of lymph nodes involved on pathologic analysis and HPV status. A high proportion of HPV-positive oropharyngeal tumors may explain the favorable outcomes observed.

Reference: Weinstein GS, Quon H, Newman HJ, et al. Transoral robotic surgery alone for oropharyngeal cancer: an analysis of local control. Arch Otolaryngol Head Neck Surg. 2012;138(7):628-634.

—Reviewed by Christine G. Gourin, MD

Swallowing Exercises During Cancer Treatment Help Muscle Maintenance

Does preventive swallowing intervention reduce the incidence of dysphagia in patients undergoing chemoradiation for head and neck cancer?

Background: Pharyngoesophageal dysfunction is common after chemoradiation for head and neck cancer and results in dysphagia due to radiation-induced tissue fibrosis, muscle disuse and muscle atrophy. Aggressive treatment using weight-loading exercises has been shown to improve strength and work capacity in previously weakened muscles. It is unclear if strength-training exercises aimed at the swallowing musculature can mitigate the effects of chemoradiation in the occurrence of dysphagia-related complications.

Study design: Randomized controlled clinical trial.

Setting: University of Florida, Gainsville.

Synopsis: Fifty-eight patients undergoing chemoradiation for head and neck cancer were randomized to one of three groups: usual care, sham swallowing intervention or active high-intensity swallowing exercise therapy treatment—termed “pharyngocise.” The intervention groups were treated daily during chemoradiation. The primary outcome measures were six-month post-treatment muscle size and composition as determined by T2-weighted MRI imaging, functional swallowing ability, dietary intake, chemosensory function, salivation, nutritional status and the occurrence of dysphagia-related complications. Patients randomized to the active swallowing program group demonstrated significantly less structural muscle deterioration in the genioglossus, hyoglossus and mylohoid muscles by MRI and greater preservation of functional swallowing, mouth opening, chemosensory acuity and salivation compared with the usual care and sham swallowing intervention groups. A composite measure was designed to designate a favorable swallowing-related outcome and included weight loss of less than 10 percent, maintenance of oral diet and a change of fewer than 10 points on the Mann Assessment of Swallowing Ability. The active treatment group was associated with six-fold greater odds of a favorable outcome after chemoradiation compared with patients who did not receive preventive exercises (p=0.009).

Bottom line: A prophylactic program of swallowing exercises during chemoradiation results in superior muscle maintenance and functional swallowing ability. Preventive swallowing therapy by a speech language pathologist should begin at the point of diagnosis and continue throughout non-operative treatment.

Reference: Carnaby-Mann G, Crary MA, Schmalfuss I, Amdur R. “Pharyngocise”: randomized controlled trial of preventative exercises to maintain muscle structure and swallowing function during head-and-neck chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2012;83(1):210-219.

—Reviewed by Christine G. Gourin, MD

Better Analytic Tools Needed for Pediatric OSA

What is the accuracy of current diagnostic clinical symptoms and signs in predicting pediatric obstructive sleep apnea (OSA)?

Background: Pediatric OSA is a severe condition that differs from its adult counterpart in physiology, clinical presentation, polysomnographic characteristics and outcomes. Although polysomnography is the gold standard for diagnosis and quantification, it requires an overnight stay in the laboratory for both parents and child. However, access to a sleep laboratory is limited in some areas. Therefore, pediatric OSA is often still diagnosed on a clinical basis.

Study design: Systematic literature review and meta-analysis.

Setting: Department of Otorhinolaryngology, Hospital Sao Sebastiao, Santa Maria da Feira; Center for Research in Health Technologies and Information Systems, University of Porto; Department of Pulmonology, Department of Pediatrics and Department of Biostatistics and Medical Informatics, Faculty of Medicine, University of Porto, Portugal.

Synopsis: Ten studies (1,525 patients) comparing the clinical assessment with polysomnography were included. Summary estimates of diagnostic accuracy used the sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and hierarchical summary receiver operating characteristic (HSROC) model. Substantial variation was found in the sensitivity and specificity among different symptoms and signs, as well as across studies. For example, tonsillar size and snoring reported by parents or caregivers had relatively high sensitivity but low specificity. In contrast, excessive daytime somnolence, observed apnea and difficulty breathing during sleep had relatively high specificity but low sensitivity.

Bottom line: Both single symptoms and combinations of symptoms and signs have poor diagnostic accuracy in predicting pediatric OSA.

Reference: Certal V, Catumbela E, Winck JC, Azevedo I, Teixeira-Pinto A, Costa-Pereira A. Clinical assessment of pediatric obstructive sleep apnea: a systemic review and meta-analysis. Laryngoscope. 2012;122(9):2105-2114.

—Reviewed by Sue Pondrom

Individualized Education Improves Language Skills in UHL

Do language skills and education performance improve or worsen over time in children?

Background: Unilateral hearing loss (UHL) affects an increasing number of children as they grow older, from one in 1,000 newborns to one in five adolescents. Given the overall dearth of knowledge about the longitudinal effects of UHL in children, this study sought to determine whether speech-language and educational performance increased or decreased over a three-year period in 46 children ages 6 to 12 years.

Study design: Prospective longitudinal cohort.

Setting: Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis; and St. Louis University School of Public Health, Mo.

Synopsis: The children were studied using standardized cognitive, achievement and language testing at yearly intervals for three years. Secondary outcomes included behavioral issues, individualized education plans (IEPs), receipt of speech therapy and teacher report of problems at school. Out of the 46 children, 39 percent had received speech therapy, 54 percent had an IEP, and 36 percent had additional educational assistance. About half had tried some form of amplification, but none wore a bone-anchored hearing aid.

Although there was no change in the achievement test mean scores, verbal and full IQ, oral expression scale and oral composite scale mean scores increased significantly. The authors said improvement in language scores and verbal IQ may be attributable to catch-up, regression to the mean or practice effects. Vocabulary T scores showed a trend toward increase, while rates of IEPs, speech therapy and behavioral issues did not decrease over time. The authors said increases in language scores did not appear sufficient to improve academic performance. Limitations to the study included lack of a control group of normal hearing children and the short period of time children were followed.

Bottom line: Children with UHL demonstrated improvement in language scores and verbal IQ over time but not in test scores or school performance.

Reference: Lieu JEC, Tye-Murray N, Fu Q. Longitudinal study of children with unilateral hearing loss. Laryngoscope. 2012;122(9):2088-2095.

—Reviewed by Sue Pondrom

Vitamin A Not an Effective Treatment for Olfactory Disorders

Is vitamin A an effective treatment for post-infectious and post-traumatic smell disorders?

Background: Olfactory dysfunction, involving a decreased or absent sense of smell, has been associated with diseases such as viral infections of the upper respiratory tract, chronic rhinosinusitis and head injuries. Only a few studies have looked at the use of prednisolone or intensive stimulation of the olfactory system as treatments. Vitamin A was chosen for this study for its potential to stimulate regeneration and repair of the peripheral olfactory system.

Study design: Double-blind, randomized, placebo-controlled clinical trial.

Setting: Department of Otorhinolaryngology, University of Dresden Medical School, Germany.

Synopsis: In 52 patients ages 20 to 70, the authors utilized the Sniffin’ Sticks test kit to measure odor thresholds, odor discrimination and odor identification (TDI scores). Vitamin A was prescribed at a dose of 10,000 for three months and follow-up testing was performed, on average, five months after the first investigation. Overall, 44 percent of all patients reported an improvement in olfactory function. There was no significant difference between placebo and vitamin A groups in TDI scores. Etiology (post-infectious or post-traumatic) had no influence on the TDI change between groups. The authors noted that a previous study by Duncan and Briggs showed an improvement in olfactory function, with dosages at 50,000 to 150,000 IU per day. The authors of this study said they could not rule out that a higher dosage of vitamin A may have a beneficial effect, but they worried about the possible side effects.

Bottom line: The applied dosage and duration of vitamin A in this study cannot be recommended in the treatment of post-infectious and post-traumatic olfactory dysfunction.

Reference: Reden J, Lill K, Zahnert T, Haehner A, Hummel T. Olfactory function in patients with postinfectious and posttraumatic smell disorders before and after treatment with vitamin A: a double-blind, placebo-controlled, randomized clinical trial. Laryngoscope. 2012;122(9):1906-1909.

—Reviewed by Sue Pondrom

ECD as Alternative Surgery for Benign Parotid Tumors

Is extracapsular dissection (ECD) an option for the resection of certain benign parotid tumors, and what are the complication rates and effectiveness of ECD versus superficial parotidectomy (SP)?

Background: ECD differs from classic enucleation, which involves the incision and shelling out of the contents of the tumor capsule. In ECD, the dense parotid fascia overlying the tumor is sharply incised followed by a blunt dissection to the level of the tumor. Under magnified visualization, a loose areolar plane may be seen 2 to 3 mm adjacent to the tumor and is the preferred plane of dissection. Careful dissection continues along the tumor capsule to prevent rupture of the small outpouchings of the tumor that may be encountered. Superficial and/or partial parotidectomy is the gold standard treatment of solitary, benign parotid tumors. SP, with special attention to the removal of the capsule to cure pleomorphic adenomas, is frequently the treatment of choice; ECD is now offered as an alternative method to

minimize the morbidity of parotidectomy.

Study design: Literature review with meta-analysis.

Setting: Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston; Department of Otorhinolaryngology, University of Erlanger-Nürnberg, Bavaria, Germany.

Synopsis: Nine studies, with 1,882 patients from five countries, were evaluated. The decision to use ECD varied among studies, but the tumors were generally superficial, clinically benign tumors of the parotid gland.

Several limited the tumor size to 2.5 cm, while others used a cutoff of 4 cm. The recurrence rates for ECD and SP were 1.5 percent and 2.4 percent, respectively. Rates of transient facial nerve paresis for ECD and SP were 8 percent and 20.4 percent, respectively. There was no difference in the rate of permanent facial nerve paralysis.

Symptomatic Frey’s syndrome was reported by 4.5 percent of ECD patients, compared with 26.1 percent of SP patients. However, the studies provided insufficient detail to determine the timing of the Frey’s syndrome evaluation, which may be relevant, because symptomatic Frey’s syndrome in the immediate post-operative period may lessen over time.

The authors noted that most of the studies did not use pre-operative imaging of fine needle aspiration cytology (FNAC). They recommended the use of FNAC and appropriate imaging in the evaluation of tumors being considered for ECD.

Bottom line: There was no difference in the rate of tumor recurrence or permanent facial paralysis between SP and ECD, while ECD appeared to have a decreased incidence of transient facial nerve palsy and Frey’s syndrome.

Reference: Albergotti WG, Nguyen SA, Zenk J, Gillespie MB. Extracapsular dissection for benign parotid tumors: a meta-analysis. Laryngoscope. 2012;122(9):1954-1960.

—Reviewed by Sue Pondrom