Surrogate endpoints in clinical trials of p16-positive squamous cell carcinoma of the oropharynx: an individual patient data meta-analysis.

BACKGROUND: The increased incidence of human papillomavirus (HPV)-related cancers has motivated efforts to optimise treatment for these patients with excellent prognosis. Validation of surrogates for overall survival could expedite the investigation of new therapies. We sought to evaluate candidate intermediate clinical endpoints in trials assessing definitive treatment of p16-positive oropharyngeal cancer with chemotherapy or radiotherapy. METHODS: We did a retrospective review of five multicentre, randomised trials (NRG/RTOG 9003, 0129, 0234, 0522, and 1016) that tested radiotherapy with or without chemotherapy in patients (aged ≥18 years) with p16-positive localised head or neck squamous-cell carcinomas. Eight intermediate clinical endpoints were considered as potential surrogates for overall survival: freedom from local progression, freedom from regional progression, freedom from distant metastasis, freedom from locoregional progression, freedom from any progression, locoregional progression-free survival, progression-free survival, and distant metastasis-free survival. We used a two-stage meta-analytical framework, which requires high correlation between the intermediate clinical endpoint and overall survival at the patient level (condition 1), and high correlation between the treatment effect on the intermediate clinical endpoint and the treatment effect on overall survival (condition 2). For both, an r2 greater than 0·7 was used as criteria for clinically relevant surrogacy. FINDINGS: We analysed 1373 patients with oropharyngeal cancer from May 9, 2020, to Nov 22, 2023. 1231 (90%) of patients were men, 142 (10%) were women, and 1207 (88%) were White, with a median age of 57 years (IQR 51-62). Median follow-up was 4·2 years (3·1-5·1). For the first condition, correlating the intermediate clinical endpoints with overall survival at the individual and trial level, the three composite endpoints of locoregional progression-free survival (Kendall's τ 0·91 and r2 0·72), distant metastasis-free survival (Kendall's τ 0·93 and r2 0·83), and progression-free survival (Kendall's τ 0·88 and r2 0·70) were highly correlated with overall survival at the patient level and at the trial-group level. For the second condition, correlating treatment effects of the intermediate clinical endpoints and overall survival, the composite endpoints of locoregional progression-free survival (r2 0·88), distant metastasis-free survival (r2 0·96), and progression-free survival (r2 0·92) remained strong surrogates. Treatment effects on the remaining intermediate clinical endpoints were less strongly correlated with overall survival. INTERPRETATION: We identified locoregional progression-free survival, distant metastasis-free survival, and progression-free survival as surrogates for overall survival in p16-positive oropharyngeal cancers treated with chemotherapy or radiotherapy, which could serve as clinical trial endpoints. FUNDING: NRG Oncology Operations, NRG Oncology SDMC, the National Cancer Institute, Eli Lilly, Aventis, and the University of Michigan.

Pathologic complete response following low-dose radiation for advanced oral cavity cancer in a patient with human immunodeficiency virus.

BACKGROUND: Advanced squamous cell carcinoma (SCCa) of the oral cavity is often not amenable to curative-intent therapy due to tumor location, tumor size, or comorbidities. CASE PRESENTATION: A 51-year-old male patient with human immunodeficiency virus and on highly active antiretroviral therapy (HAART) presented with a cT4aN2c SCCa of the tongue. He received a preoperative single course of Quad-Shot radiation therapy to 14 Gy in 4 fractions followed by surgical resection. Patient had no residual carcinoma on surgical pathology and no evidence of disease on subsequent clinical and radiological exams. CONCLUSIONS: To our knowledge, this is the first case of pathologic complete response for a patient on HAART following a single cycle of the Quad-Shot regimen for advanced oral cavity SCCa. Protease inhibitors in HAART can induce spontaneous tumor regression via inhibition of proteasome function and activation of apoptosis, and thus act as a cancer therapeutic.

Tobacco cessation after head and neck cancer diagnosis is an independent predictor of treatment response and long-term survival.

Head and neck squamous cell carcinoma (HNSCC) patients who are current smokers when diagnosed have inferior clinical outcomes compared to never-smokers or previous smokers. However, the impact of quitting after HNSCC diagnosis has not been quantified. In this retrospective, case-control study (n = 134), the odds of complete response to first-line therapy were 3.7 times higher among smokers at diagnosis who quit before treatment initiation (quitters; n = 55) than among those continuing to smoke (p = 0.03). Disease-free survival was also higher among quitters (aHR, 0.33; 95 % CI, 0.12-0.90; p = 0.029). Quitters were 67 % less likely to die of all causes than active smokers (aHR, 0.33; 95 % CI, 0.15-0.71; p = 0.004). These data show for the first time that, smoking cessation after HNSCC diagnosis is predictive of higher therapy efficacy and long-term survival.

Primary Dural Repair Using Titanium Microclips Following Lateral Skull Base Surgery.

Objective Standard techniques for primary dural repair following lateral skull base surgery are both technically challenging and time consuming without the potential for primary dural repair. Inadequate closure may result in postoperative cerebrospinal fluid (CSF) leak infectious sequalae. Traditional methods of dural repair rely on secondary obliteration of the CSF fistula. We hypothesized that the use of nonpenetrating titanium microclips may serve as a useful adjunct in primary dural repair or the establishment of an immobile repair layer following lateral skull base surgery. Methods Here, we report a novel technique for primary dural repair using nonpenetrating titanium microclips as an adjunct to standard techniques in a series of six patients with lateral skull base pathologies. Results A total of six consecutive lateral skull base tumor patients with titanium microclip dural reconstruction were included in our case series. Lateral skull base pathologies represented in this group included two jugular foramen schwannomas, one vestibular schwannoma, one petroclival meningioma, one glomus jugulare paraganglioma, and one jugular foramen chordoid meningioma. Conclusion To our knowledge, this is the first report on the use of microclips in repairing dural defects following lateral skull base surgery. Surgical outcomes for this small case series suggest that dural repair of the later skull base with nonpenetrating titanium microclips is a useful adjunct in dural repair following lateral skull base surgery.

Neoadjuvant QUAD shot for downstaging or temporizing locally advanced oral cavity cancer prior to definitive surgery.

OBJECTIVES: The mainstay of oral cavity cancer treatment is surgery, often with adjuvant therapies. However, patients often present with locally advanced disease and downstaging would render surgery more feasible. We evaluated hypofractionated radiation therapy (QUAD Shot) prior to definitive surgery for head and neck cancers, with a goal of downstaging. MATERIALS AND METHODS: Eighteen patients with primary head and neck malignancy, predominantly locally advanced oral cavity cancers, received QUAD Shot radiation therapy from June 2016 to July 2021. External beam radiation therapy was delivered to the primary lesion in four fractions over two days, two fractions/day at least six hours apart with total dose ranging from 1400 cGy to 1500 cGy. Twelve patients proceeded to definitive surgery. RESULTS: Of the twelve patients receiving surgery, one had complete response to radiation therapy with no pathological disease seen at surgery. Four patients had a partial response, defined as downstaging on final pathology. Five patients showed no response, and two had progressive disease defined as upstaging on final pathology. Seven patients had radiographic primary tumor shrinkage ≥ 0.5 cm following Quad Shot. The Quad Shot was tolerated well with no reported adverse effects. CONCLUSION: Discrepancies between clinical- and pathological-staging are common and expected. However, ∼40 % of our patients experienced downstaging following QUAD Shot. Thus, neoadjuvant radiation therapy may be viable for temporizing tumor growth while awaiting surgery, or for downstaging and thus facilitating more technically feasible and less morbid surgery for locally advanced head and neck cancers.

Merkel cell carcinoma: treatment and outcomes over a 10-year period at a high-volume academic center.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, highly aggressive malignancy which lacks high-level evidence-based treatment guidelines. METHODS: To determine outcomes of MCC patients and assess the role of radiation in treatment, we performed a retrospective chart review of patients treated for MCC between 2006 and 2016 at a single high-volume academic medical center. The primary outcome was overall survival (OS) for the entire population and for those populations receiving specific therapies. RESULTS: Forty-two patients were evaluable. OS for all patients was not reached since most remain alive at time of analysis. OS for the American Joint Committee on Cancer (AJCC) stage I was not reached. OS for stages II, III, and IV was 37.3 months (6.8, -), 49.5 months (14.2, 49.5), and 14.5 months (10.8, -), respectively. OS could not be reached in the high radiotherapy (RT) dose group (biologically equivalent dose [BED] ≥ 60) and was 49.5 months (10.8, -) in the low-dose group (BED < 60). For surgical margin status, OS was 14.9158 months (6.8008, -) for positive margins and 37.3 months (10.8, -) for negative margins. CONCLUSIONS: No conclusive findings for OS were identified; however, trends for improved OS were associated with lower AJCC staging, negative surgical margins, and high RT doses.

Primary hyperparathyroidism: Disease of diverse genetic, symptomatic, and biochemical phenotypes.

Genetic, symptomatic, and biochemical heterogeneity of patients with primary hyperparathyroidism (PHPT) has become apparent in recent years. An in-depth, evidence-based review of the phenotypes of PHPT was conducted. This review was intended to provide the resulting information to surgeons who operate on patients with hyperparathyroidism. This review revealed that the once relatively clear distinction between familial and sporadic PHPT has become more challenging by the finding of various germline mutations in patients with seemingly sporadic PHPT. On the one hand, the genetic and clinical characteristics of some syndromes in which PHPT is an important component are now better understood. On the other hand, knowledge is emerging about novel syndromes, such as the rare multiple endocrine neoplasia type IV (MEN4), in which PHPT occurs frequently. It also revealed that, currently, the classical array of symptoms of PHPT is seen rarely upon initial presentation for evaluation. More common are nonspecific, nonclassical symptoms and signs of PHPT. In areas of the world where serum calcium levels are checked routinely, most patients today are "asymptomatic" and they are diagnosed after an incidental finding of hypercalcemia; however, some of them have subclinical involvement of bones and kidneys, which is demonstrated on radiographs, ultrasound, and modern imaging techniques. Last, the review points out that there are three distinct biochemical phenotypes of PHPT. The classical phenotype in which calcium and parathyroid hormone levels are both elevated, and other disease presentations in which the serum levels of calcium or intact parathyroid hormone are normal. Today several, distinct phenotypes of the disease can be identified, and they have implications in the diagnostic evaluation and treatment of patients, as well as possible screening of relatives.

Commentary on the management of total laryngectomy patients during the COVID-19 pandemic.

The coronavirus disease-2019 (COVID-19) pandemic has rapidly spread across the world, placing unprecedented strain on the health care system. Health care resources including hospital beds, ICUs, as well as personal protective equipment are becoming increasingly rationed and scare commodities. In this environment, the laryngectomee (patient having previously undergone a total laryngectomy) continues to represent a unique patient with unique needs. Given their surgically altered airway, they pose a challenge to manage for the otolaryngologist within the current COVID-19 pandemic. In this brief report, we present special considerations and best practice recommendations in the management of total laryngectomy patients. We also discuss recommendations for laryngectomy patients and minimizing community exposures.

Anterior cervical discectomy and fusion requiring resection of the superior horn of thyroid cartilage: case report.

Anterior cervical discectomy and fusion (ACDF) is the most common surgical procedure utilized for degenerative diseases of the cervical spine. The authors present the case of a 64-year-old man who underwent an ACDF for degenerative changes causing cervical stenosis with myelopathy. The patient's symptoms consisted of pain and weakness of the bilateral upper extremities that slowly progressed over 1.5 years. During the procedure, the superior horn of the thyroid cartilage impeded proper retraction, preventing adequate visualization due to its prominent size. At this point, otorhinolaryngology was consulted, which allowed for safe resection of this portion of the thyroid cartilage while preserving nearby critical structures. With the frequent usage of this surgical approach for various etiologies, the importance of proper recognition and consultation is paramount. Encountering prominent thyroid cartilage resulting in surgical obstruction has not been described in the literature and this report represents a paradigm for the proper course of action.

Does perioperative oxandrolone improve nutritional status in patients with cachexia related to head and neck carcinoma?

BACKGROUND: Cancer cachexia affects up to over 50% of advanced head and neck cancer (HNC) patients. To date, the potential utility of anabolic steroids in perioperative cachectic HNC patients has not been determined. METHODS: Retrospective review of pre- and post-oxandrolone administration prealbumin levels in 18 perioperative HNC patients between October 2007 and October 2014 at a tertiary academic medical center. RESULTS: The median pretreatment prealbumin was 88.5 mg/L. The median post-treatment prealbumin was 227 mg/L. The median interval improvement of the prealbumin level was 131.5 mg/L. The median differences between the pretreatment and post-treatment prealbumin levels were found to be statistically significant (P < .001). Subjective improvement in wound healing was also observed. CONCLUSIONS: Perioperative administration of oxandrolone resulted in objective improvements in prealbumin levels and subjective improvements in surgical wounds. Oxandrolone administered 10 mg twice daily (BID) for 10 days may be a useful adjunct in the perioperative care of nutritionally deficient HNC patients who are at risk for or have demonstrated impaired wound healing. LEVEL OF EVIDENCE: 3.

Ultrasound-Guided Fine-Needle Aspiration With Optional Core Needle Biopsy of Head and Neck Lymph Nodes and Masses: Comparison of Diagnostic Performance in Treated Squamous Cell Cancer Versus All Other Lesions.

OBJECTIVES: To evaluate the diagnostic performance of ultrasound (US)-guided fine-needle aspiration with optional core needle biopsy of head and neck lymph nodes and masses, with attention to differences between biopsy of treated squamous cell carcinoma (SCC) and biopsy of other lesions. METHODS: Institutional Review Board approval was obtained, and the need for consent was waived for this retrospective study. All 861 US-guided biopsies of head and neck lymph nodes and masses performed between March 1, 2012, and May 16, 2016, were reviewed. RESULTS: Of the 861 biopsies, 53 targeted SCC with residual masses after treatment. The biopsy procedures yielded benign or malignant pathologic results in 71.7% (38 of 53) of treated SCC and 90.7% (733 of 808) of all other lesions (P < .001). A reference standard based on subsequent pathologic results or clinical and imaging follow-up was established in 68.4% of procedures. In cases with benign or malignant biopsy results and a subsequent reference standard, the sensitivity values for malignancy were 87.5% (95% confidence interval, 64.0%-96.5%) in treated SCC and 98.3% (95% confidence interval, 96.0%-99.3%) in all other cases (P = .047), and the specificity values were 63.6% (95% confidence interval, 35.4%-84.8%) in treated SCC and 99.5% (95% confidence interval, 97.3%-99.9%) in all other cases (P < .001). There were no major complications related to the biopsy procedures. CONCLUSIONS: Excluding treated SCC, US-guided fine-needle aspiration with optional core needle biopsy of head and neck lymph nodes and masses has excellent diagnostic performance. Needle biopsy of head and neck SCC with a residual mass after therapy has a high rate of nondiagnostic samples, suboptimal sensitivity, and poor specificity.

Selective patient experience with the Blom-Singer Dual Valve voice prosthesis.

OBJECTIVES/HYPOTHESIS: This study compares the overall durability, phonation effort, and speech quality achieved by the Blom-Singer Dual Valve prosthesis to the same characteristics achieved by the single-valve prosthesis used in a select population of total laryngectomy patients who have demonstrated single-valve prosthesis failure within 3 months of placement. STUDY DESIGN: Prospective phase IV study. METHODS: Fourteen patients who had previously experienced early valve failure using a single-valve prosthesis had a Dual Valve placed by a speech language pathologist. A total of seventeen Dual Valves were inserted during routine clinical visits for valve replacement. Time intervals from insertion to replacement of the Dual Valve, as well as the average lifespan of patients' three previous single valves were collected. Subjective, categorical responses to speech quality and phonation effort for the Dual Valve compared to the single valve were collected on a questionnaire upon failure of the device. RESULTS: The mean duration of the single valve was 60 days, with a median of 51 days, whereas the mean duration of the Dual Valve was 164 days, with a median duration of 84 days. Both sets of data were statistically significant, with a P value of .0131. Valve life was increased in 86% of patients, with 43% experiencing greater than 150 days improvement in valve duration when using the Dual Valve. Phonation effort was increased in 14% of patients, and speech quality was not significantly affected in any patients. CONCLUSIONS: In this select population, the Dual Valve offers improved durability over the single valve without sacrificing speech quality, making it a preferred prosthesis option for patients experiencing single-valve failure in less than 3 months. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:422-426, 2018.

Fine-needle aspiration with selective use of core needle biopsy of major salivary gland tumors.

OBJECTIVES: Preferential use of fine-needle aspiration (FNA) versus core needle biopsy (CNB) for distinguishing benign from malignant major salivary gland tumors is highly debated. The main disadvantage of FNA is lower sensitivity, whereas arguments against CNB include use of a larger bore needle and greater risk of complications. The aim of this study is to evaluate our experience performing ultrasound-guided (UG) FNA with selective use of CNB based on preliminary cytopathology, and to determine whether our preoperative diagnostic approach is more sensitive and specific than FNA alone-and at least as sensitive and specific as CNB alone. STUDY DESIGN: Retrospective review of UG needle biopsy sampling of lesions arising in or around parotid and submandibular glands. METHODS: Ultrasounds of 141 needle biopsies were identified. Patient/lesion/needle biopsy characteristics, preliminary cytopathology, final pathology, imaging studies, and subsequent clinical course and treatment were documented. RESULTS: Needle biopsies performed according to our protocol provided results that guided clinical decision making in 125 of 135 cases, 92.6% (95% confidence interval [CI], 86.8%-96.4%) of the time. Using 41 cases that had histologic verification, sensitivity was 100% (95% CI, 79.6%-100%), and specificity was 92.3% (95% CI, 75.9%-97.9%) for detecting malignancy. We definitively characterized 120 lesions as benign (84) or malignant (36). CONCLUSION: Preoperative needle biopsy diagnoses allowed clinical management to progress 92.6% of the time. The protocol of FNA with selective use of CNB may potentially reduce patient exposure to risks associated with CNB without the tradeoff of lower sensitivity seen with FNA. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2522-2527, 2017.

Malignant Peripheral Nerve Sheath Tumor of the C2 Nerve Root: Case Report.

Here we present the case of a 36-year-old man who was found to have a symptomatic malignant neural sheath tumor growing from the C2 nerve root following a period of progressively worsening headaches. The patient was successfully treated with surgical resection resulting in resolution of cranial nerve deficits. Though uncommon, malignant peripheral nerve sheath tumor must be considered in the differential diagnosis of tumors involving the cervical nerve roots and carotid space.

Exploratory Factor Analysis of NRG Oncology's University of Washington Quality of Life Questionnaire-RTOG Modification.

CONTEXT: The 15-item University of Washington Quality of Life questionnaire-Radiation Therapy Oncology Group (RTOG) modification (UW-QOL-RTOG modification) has been used in several trials of head and neck cancer conducted by NRG Oncology such as RTOG 9709, RTOG 9901, RTOG 0244, and RTOG 0537. OBJECTIVES: This study is an exploratory factor analysis (EFA) to establish validity and reliability of the instrument subscales. METHODS: EFA on the UW-QOL-RTOG modification was conducted using baseline data from NRG Oncology's RTOG 0537, a trial of acupuncture-like transcutaneous electrical nerve stimulation in treating radiation-induced xerostomia. Cronbach α coefficient was calculated to measure reliability; correlation with the University of Michigan Xerostomia Related Quality of Life Scale was used to evaluate concurrent validity; and correlations between consecutive time points were used to assess test-retest reliability. RESULTS: The 15-item EFA of the modified tool resulted in 11 items split into four factors: mucus, eating, pain, and activities. Cronbach α ranged from 0.71 to 0.93 for the factors and total score, consisting of all 11 items. There were strong correlations (ρ ≥ 0.60) between consecutive time points and between total score and the Xerostomia Related Quality of Life Scale total score (ρ > 0.65). CONCLUSION: The UW-QOL-RTOG modification is a valid tool that can be used to assess symptom burden of head and neck cancer patients receiving radiation therapy or those who have recently completed radiation. The modified tool has acceptable reliability, concurrent validity, and test-retest reliability in this patient population, as well as the advantage of having being shortened from 15 to 11 items.

Xerostomia health-related quality of life: NRG oncology RTOG 0537.

PURPOSE: The purpose of this secondary analysis was to determine change in overall health-related quality of life (HRQOL) based on patient data obtained from NRG Oncology RTOG 0537 as measured by the RTOG-modified University of Washington Head and Neck Symptom Score (RM-UWHNSS). METHODS: A multi-site prospective randomized clinical trial design stratified 137 patients with post-radiation therapy xerostomia according to prior pilocarpine (PC) treatment and time after radiation therapy and/or chemotherapy and randomized patients into two groups. Patients were assigned to acupuncture or PC. Twenty-four sessions of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) were administered over 12 weeks, or oral PC (5 mg) three times daily over the same 12 weeks. The RM-UWHNSS was administered at baseline and at 4, 6, 9, and 15 months after the date of randomization. RESULTS: There were no between-arm differences in change scores on the RM-UWHNSS in the individual items, total score, or factor scores. For statistical modeling, race and time were significant for all outcomes (total and factor scores), while treatment arm was not significant. The ALTENS arm showed greater yet nonsignificant improvement in outcomes compared to the PC arm. CONCLUSION: Although no significant treatment differences were seen in this trial, patients receiving ALTENS consistently had lower scores, indicating better function, as compared to those receiving PC. Radiation-induced xerostomia improved over time for all patients.

Fistula rates after salvage laryngectomy: comparing pectoralis myofascial and myocutaneous flaps.

OBJECTIVES/HYPOTHESIS: Salvage laryngectomy after failed organ preservation often has a high complication rate, pharyngocutaneous fistulas being the most common. These fistulas increase morbidity, prolong hospitalization, and potentially delay adjuvant treatment. Fistula rates in the literature range from 3% to 65%. Use of the pectoralis flap to prevent fistula formation has been adopted as a common practice at our institution. A review of our experience using the overlay myofascial showed a higher than desired complication rate. The aim of this study is to assess whether the use of integrated myocutaneous flap results in a lower fistula rate. STUDY DESIGN: A retrospective review of 30 patients followed by a pilot study of 10 patients. All underwent salvage laryngectomy after failed organ preservation. METHODS: The operation notes of 40 laryngectomy patients were analyzed. The patient/tumor characteristics, pretreatment, neck dissection, flap type, and fistula rate were documented. RESULTS: The patient sample was 25% female. All patients received prior radiotherapy, but only 37.5% received prior chemoradiation. Neck dissections were performed in 80% of these patients, 76% of the myocutaneous group, and 84% of the myofascial group. Advanced tumor stage was found in 42% of the myofascial group and 52% of the myocutaneous group. Five of the 19 myofascial patients developed a fistula, whereas seven of the 21 myocutaneous patients developed a fistula. CONCLUSIONS: The use of the pectoralis myocutaneous flap (PMCF) in this pilot series did not show a lower rate of fistula; other alternatives should be pursued to decrease this complication. LEVEL OF EVIDENCE: 4.

Prophylactic PEG placement in head and neck cancer: how many feeding tubes are unused (and unnecessary)?

AIM: To determine the rate of use and non-use of prophylactic percutaneous endoscopic gastrostomy (PEG) tubes among patients with head and neck cancer (HNC) patients. METHODS: All patients with HNC undergoing PEG between January 1, 2004 and June 30, 2006 were identified. Patients (or their next-of-kin) were surveyed by phone and all available medical records and cancer registry data were reviewed. Prophylactic PEG was defined as placement in the absence of dysphagia and prior to radiation or chemoradiation. Each patient with a prophylactic PEG was assessed for cancer diagnosis, type of therapy, PEG use, and complications related to PEG. RESULTS: One hundred and three patients had PEG tubes placed for HNC. Thirty four patients (33%) could not be contacted for follow-up. Of the 23 (22.3%) patients with prophylactic PEG tubes, 11/23 (47.8%) either never used the PEG or used it for less than 2 wk. No association with PEG use vs non-use was observed for cancer diagnosis, stage, or specific cancer treatment. Non-use or limited use was observed in 3/6 (50%) treated with radiation alone vs 8/17 (47.1%) treated with chemoradiation (P = 1.0), and 3 of 10 (30%) treated with surgery vs 8 of 13 (62%) not treated with surgery (P = 0.21). Minor complications were reported in 5/23 (21.7%). One (4.3%) major complication was reported. CONCLUSION: There is a high rate of unnecessary PEG placement when done prophylactically in patients with head and neck cancer.

Hyaluronic acid hydrogel sustains the delivery of dexamethasone across the round window membrane.

BACKGROUND: The use of intratympanic (IT) steroids for the treatment of inner ear disorders is promising, but the clinical challenges of prolonged middle ear drug application have proven burdensome, and a sustainable delivery system is yet to be developed. METHOD: In this study, a guinea pig model was used to determine if dexamethasone in combination with a hyaluronic-acid (HA)-based hydrogel is an efficient, stable and sustainable dexamethasone delivery system to the inner ear. For each animal, right and left middle ear bullae were randomly selected to be filled with dexamethasone alone or dexamethasone-HA (Dex-HA) gel. Perilymph samples were collected at different time points and dexamethasone levels were determined using an ELISA. RESULTS: Dexamethasone was measurable in the perilymph samples up to 72 h after treatment. At 24 h after treatment, the perilymph dexamethasone concentrations were significantly higher (p = 0.01) in the ears treated with Dex-HA gel than in those treated with dexamethasone alone. While the perilymph dexamethasone concentration had decreased at 48 h after treatment with Dex-HA gel, the levels were still higher than those observed at 24 h in ears treated with dexamethasone alone. A high variability in dexamethasone concentration was observed between the samples, and the variability between matched ears receiving different treatments was remarkably lower than the variability within each treatment group, suggesting that individual parameters might play a major role in perilymph dexamethasone concentration. There was no statistically significant correlation between dexamethasone concentration and sex, weight or laterality. CONCLUSIONS: Our results show that the Dex-HA gel used in this study provides an effective and sustained dexamethasone release mechanism that might be utilized to treat conditions such as sudden sensorineural hearing loss. This could potentially reduce the morbidity and costs associated with IT treatment.