JAMA otolaryngology-- head & neck surgery最新文献

Importance: Neoadjuvant immunotherapy shows promise in the treatment of head and neck squamous cell carcinoma (HNSCC). Pathologic treatment effect (pTE) is one way to assess response to treatment; however, the association of this response with survival outcomes is not yet clear. The current study sought to determine whether treatment response to neoadjuvant nivolumab, as measured by pTE, correlates with survival outcomes.

Objective: To determine whether patients with HNSCC with pathologic response to neoadjuvant nivolumab have improved survival outcomes.

Design, setting, and participants: A cohort study performing a pooled analysis of 2 multi-institutional neoadjuvant clinical trials (NCT03238365, NCT03854032) enrolling patients from July 2017 to January 2022, was performed. Patients with resectable HNSCC enrolled in 1 of 2 clinical trials and treated with neoadjuvant immunotherapy and surgical resection were included in the analysis. Patients were followed up for a median (range) of 36 (4-72) months. Analysis took place on April 15, 2024.

Intervention: Patients were treated with neoadjuvant nivolumab with or without the addition of immunomodulating medications (tadalafil or indoleamine 2,3 dioxygenase inhibitor).

Main outcome and measure: Pooled analysis was performed to plot Kaplan-Meier 3-year survival outcomes for pTE responders and low or nonresponders. A pTE response threshold was determined using recursive partitioning analysis.

Results: Seventy-nine patients were included in the analysis, of whom 40 (51%) had human papillomavirus (HPV)-negative disease. Recursive partitioning analysis identified a pTE threshold of 57%, which was used to define pathologic responders vs low or nonresponders. Pathologic responders with HPV-negative disease had significantly improved disease-free survival (100% for responders vs 66.8% for low or nonresponders; 95% CI, 46.1%-80.6%) and overall survival (100% for responders vs 73.3% for low or nonresponders; 95% CI, 53.4%-85.7%). In patients with HPV-positive disease, disease-free survival was high for both responders (90%; 95% CI, 47.3%-98.5%) and low or nonresponders (92.4%; 95% CI, 72.8%-98.1%).

Conclusion and relevance: This cohort study found that patients with HPV-negative disease who are deemed pathologic responders (pTE >57%) to neoadjuvant nivolumab may have improved survival outcomes compared with those who are low or nonresponders. Not only does this suggest a role for using pathologic response as a surrogate marker, but it further highlights the neoadjuvant strategy in HNSCC as associated with improved survival.

Importance: Osteoradionecrosis (ORN) is a potentially debilitating late complication of radiotherapy (RT) for head and neck cancer. While proton therapy offers superior dose conformality, its impact on ORN risk remains uncertain, particularly in patients with oropharyngeal squamous cell carcinoma (OPSCC).

Objective: To characterize the incidence, severity, and predictors of ORN in a large institutional cohort of patients with OPSCC treated with curative-intent RT, and to compare outcomes between proton therapy and intensity-modulated radiation therapy (IMRT).

Design, setting, and participants: This retrospective cohort study included consecutive patients with OPSCC treated from January 2013 to December 2023 at a single high-volume academic institution. Patients received either IMRT or proton therapy (uniform scanning or pencil beam scanning). ORN diagnosis and grading were determined through standardized multidisciplinary review. The primary outcome was the 3-year rate of ORN. Cox regressions identified predictors of ORN. Data were analyzed from December 2024 to April 2025.

Exposures: Radiotherapy modality (proton vs IMRT), patient demographic characteristics, smoking status, human papillomavirus status, tumor and/or node stage, chemotherapy, and radiation dosage.

Results: The analysis included 1564 patients (mean [SD] age, 61.5 [9.6] years; 208 females [13.3%] and 1356 males [86.7%]) of whom 1389 patients (88.8%) had undergone IMRT, and 175 patients (11.2%) had undergone proton-based treatment. The 3-year incidence of any-grade ORN was 3.02% (95% CI, 2.22%-4.09%). ORN rates were significantly higher after proton therapy compared with IMRT (6.36% vs 2.69% at 3 years; hazard ratio [HR], 2.62; 95% CI, 1.39-4.93). Of 1344 definitive patients, 47 of 1210 patients in the IMRT group (3-year rate, 2.38%; 95% CI, 1.61-3.51%) developed ORN vs 11 of 134 patients in the proton group (3-year rate 7.47%; 95% CI, 3.40-16.02% [HR, 3.62; 95% CI, 1.85-7.09]). On multivariable analysis, proton therapy (HR, 2.92; 95% CI, 1.55-5.50), concurrent chemotherapy (HR, 3.29; 95% CI, 1.03-10.50), and smoking (HR, 2.33; 95% CI, 1.38-3.92) were independently associated with ORN. Grade 3 or greater ORN occurred in 0.67% of patients and did not appear to differ by RT modality.

Conclusions and relevance: In this large, relatively homogeneous cohort of patients with OPSCC, proton therapy was associated with a higher rate of ORN compared with IMRT, particularly in the definitive setting, although high-grade ORN remained uncommon across both modalities. These retrospective findings should be considered exploratory and underscore the need for future hypothesis-driven studies to refine dose constraints and optimize treatment planning to mitigate ORN risk among patients with OPSCC.

Importance: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become substantially more popular as a medication to treat obesity and type 2 diabetes (T2D). Despite their known association with gastroesophageal reflux disease and vagal nerve stimulation, the association between GLP-1RAs and chronic cough has not been previously studied.

Objective: To assess the clinical association between GLP-1RAs and chronic cough.

Design, setting, and participants: This large, multicenter cohort study used clinical records from a US-based collection of electronic medical record data from April 28, 2005, to April 15, 2025, from 70 health care organizations. Adults (≥18 years) with T2D and prescription of a GLP-1RA were identified. Additionally, groups with T2D and prescription of another second-line diabetes medication, including dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and sulfonylureas were created. After propensity score matching for various demographic and clinical characteristics, adjusted hazard ratios (aHRs) and 95% CIs were calculated using Cox regression analyses to estimate the risk of new chronic cough or gastroesophageal reflux disease diagnosis.

Exposure: GLP-1RAs or other second-line diabetes medication.

Main outcomes and measures: Chronic cough.

Results: Cohorts included 427 555 individuals (mean [SD] age, 55.8 [13.8] years; 251 928 female individuals [58.9%]) with T2D who were prescribed a GLP-1RA and 1 614 495 individuals (mean [SD] age, 63.7 [13.3] years; 712 946 female individuals [44.4%]) with T2D who were prescribed another second-line diabetes medication. After propensity score matching, individuals prescribed a GLP-1RA had significantly increased risk of new chronic cough compared with individuals prescribed any non-GLP-1RA second-line medication (aHR, 1.12; 95% CI, 1.08-1.16), DPP-4 inhibitor (aHR, 1.18; 95% CI, 1.11-1.26), or sulfonylurea (aHR, 1.32; 95% CI, 1.24-1.40) but not compared with SLGT2 inhibitors (aHR, 1.03; 95% CI, 0.98-1.09). After removing patients with a previous diagnosis of gastroesophageal reflux disease from analysis, patients prescribed GLP-1RAs had significantly increased risk of chronic cough compared with those prescribed any non-GLP-1RA (aHR, 1.29; 95% CI, 1.17-1.42), DPP4 inhibitor (aHR, 1.36; 95% CI, 1.17-1.58), SGLT2 inhibitor (aHR, 1.14; 95% CI, 1.02-1.28), or sulfonylurea (aHR, 1.25; 95% CI, 1.09-1.42).

Conclusions and relevance: This cohort study suggests an association between GLP-1RA use and chronic cough. Further research is needed to confirm the existence, strength, and mechanisms of this association.