BACKGROUND:Salivary gland carcinomas are uncommon malignancies with various histological subtypes harboring fusion genes. The EWSR1::ATF1 fusion gene, resulting from a translocation between chromosomes 12 and 22, is frequently observed in hyalinizing clear cell carcinoma (HCCC). However, the role of this fusion gene in HCCC oncogenesis remains unclear. METHODS:We generated EWSR1::ATF1 transgenic mice by introducing an EWSR1::ATF1 fusion gene with a breakpoint in HCCC. These mice were crossed with Lama parotid secretory protein (PSP)-Cre transgenic mice, expressing Cre recombinase in salivary glands, to produce salivary gland-specific EWSR1::ATF1 transgenic mice. Tumor samples were analyzed using Western blotting, histopathology, and RNA sequencing. RESULTS:We generated salivary gland-specific EWSR1::ATF1 transgenic mice, and tumors developed in major salivary glands in three mice. These tumors exhibited more malignant characteristics than human HCCC. CONCLUSIONS:These results suggest that salivary gland-specific expression of EWSR1::ATF1 plays an important role in malignant tumor formation in major salivary glands.

The interim analysis of JCOG1008 demonstrated that chemoradiotherapy with cisplatin 40 mg/m2 once a week for seven cycles (weekly cisplatin) was noninferior in terms of overall survival (OS) compared with chemoradiotherapy with cisplatin 100 mg/m2 once every 3 weeks for three cycles (3-weekly cisplatin) for postoperative high-risk locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). This report presents the long-term follow-up results of JCOG1008. In this phase II/III trial, patients with postoperative high-risk LA-SCCHN were randomly assigned to receive either chemoradiotherapy with 3-weekly cisplatin or with weekly cisplatin. A total of 261 patients were enrolled. At the final analysis, with a median follow-up of 5.6 years, 5-year OS was 58.7% in the 3-weekly arm and 71.2% in the weekly arm (hazard ratio, 0.76 [95% CI, 0.52 to 1.12 [<1.32]]), confirming the noninferiority of the weekly regimen. Both 5-year relapse-free survival (RFS) and 5-year local RFS were numerically better in the weekly arm. No late adverse event showed more than a 10% difference between the two arms. In conclusion, 5-year follow-up confirmed that chemoradiotherapy with weekly cisplatin is noninferior in OS to chemoradiotherapy with 3-weekly cisplatin in patients with postoperative high-risk LA-SCCHN. These results further support the use of weekly cisplatin plus radiotherapy as a reasonable alternative for this patient population.

Endoscopic transnasal apicoectomy (ETA) is a novel multidisciplinary technique that combines endoscopic sinus surgery with apicoectomy via a transnasal approach. ETA enables direct access to periapical lesions while preserving the causative tooth. Our initial experience suggests that this minimally invasive approach is safe, feasible, and effective for selected cases of odontogenic maxillary sinusitis.

Based on the results of the JCOG1212 trial, superselective intra-arterial infusion chemoradiotherapy (IA-CRT) has become a standard treatment option for patients with locally advanced maxillary sinus carcinoma (LA-MSC), especially those with T4a disease, in Japan. This study aimed to evaluate the real-world effectiveness of IA-CRT compared with systemic intravenous chemoradiotherapy (IV-CRT) in patients with LA-MSC. We retrospectively analyzed data from patients with T3 and T4 N0M0 maxillary sinus carcinoma who were treated with IA-CRT or IV-CRT between 2011 and 2017, using data from the Head and Neck Cancer Registry of Japan. The primary endpoint was the 5-year local control rate (LCR), and the secondary endpoints were overall survival (OS) and progression-free survival (PFS). Survival analyses were performed using inverse probability of treatment weighting (IPTW) adjustment. Among 1,329 registered patients, 507 received definitive chemoradiotherapy as initial treatment, including 373 patients treated with IA-CRT (median follow-up, 46 months) and 134 treated with IV-CRT (median follow-up, 31 months). After IPTW adjustment, the 5-year LCR was significantly higher in the IA-CRT group than in the IV-CRT group (67.0

BACKGROUND/AIM:The first-line treatment for platinum-sensitive recurrent or metastatic head and neck cancer (R/M HNSCC) is pembrolizumab with or without chemotherapy. The decision to combine chemotherapy largely depends on programmed death-ligand 1 (PD-L1) expression; however, chemotherapy is often difficult to administer in older adult patients because of reduced physiological reserve and comorbidities. Therefore, we analyzed real-world data to evaluate the effectiveness of pembrolizumab monotherapy according to age and PD-L1 combined positive score (CPS). PATIENTS AND METHODS:This multicenter retrospective observational study analyzed the medical records of patients who received pembrolizumab monotherapy for R/M HNSCC. Patients with unknown CPS were excluded. This study was approved by our institutional review board. Overall survival (OS), progression-free survival (PFS), response rates, and immune-related adverse events were evaluated. All analyses were exploratory, and statistical significance was set at p<0.05. RESULTS:A total of 130 patients were included (median age, 72.5 years; range=40-89 years). Patients were classified into a young group (<75 years, n=75) and an older adult group (≥75 years, n=55). Median OS and PFS did not differ significantly between the young and older adult groups. Among older adult patients, those with high CPS (≥20) showed a trend toward improved OS compared with those with low CPS. Response rates and the incidence of immune-related adverse events were comparable between age groups. CONCLUSION:Pembrolizumab monotherapy demonstrated clinically meaningful real-world effectiveness and acceptable tolerability in older adult patients with R/M HNSCC, particularly in those with high PD-L1 expression (CPS≥20). In contrast, the benefit appeared limited in older adult patients with low CPS, underscoring the importance of careful patient selection and timely consideration of alternative strategies in real-world practice.

It is difficult to accurately predict occult cervical lymph node metastasis, a major factor that significantly influences treatment outcomes in patients with clinical stage I/II tongue cancer. This study aimed to develop a predictive model for occult cervical lymph node metastasis in patients with stage I/II tongue cancer based on clinical and histopathological findings. This multicenter cross-sectional study analyzed the archived pathological specimens and clinical records of patients diagnosed with stage I/II tongue cancer between January 2012 and March 2020 at seven institutions in Japan. All patients underwent transoral partial glossectomy with elective neck dissection, and the histological depth of invasion (DOI) was confirmed to be 3–10 mm. The clinicopathological features of the primary tumors were compared with those of occult cervical lymph node metastases. Predictive factors for occult cervical lymph node metastasis were identified using the least absolute shrinkage and selection operator (LASSO) regression model, and the model performance was evaluated using receiver operating characteristic (ROC) analysis. In total, 106 patients were included in this study. The LASSO regression analysis identified three significant predictors of occult cervical lymph node metastasis: vascular invasion, poorly differentiated clusters (PDC), and DOI. The predictive model incorporating these factors achieved an area under the curve (AUC) of 0.713. Vascular invasion, PDC, and DOI are the key histopathological predictors of occult cervical lymph node metastasis in early-stage tongue cancer. External validation in larger cohorts is warranted to validate the utility of the predictive model developed in this study.

BACKGROUND:The benefit of the addition of perioperative pembrolizumab to standard care with surgery and adjuvant therapy for patients with locally advanced head and neck squamous-cell carcinoma (HNSCC) is unclear. METHODS:In this phase 3, open-label trial, we randomly assigned participants with locally advanced HNSCC in a 1:1 ratio to receive 2 cycles of neoadjuvant pembrolizumab and 15 cycles of adjuvant pembrolizumab (both at a dose of 200 mg every 3 weeks) in addition to standard care (pembrolizumab group) or standard care alone (control group). Standard care was surgery and adjuvant radiotherapy with or without concomitant cisplatin. The primary end point was event-free survival, sequentially assessed in participants whose tumors expressed programmed death ligand 1 (PD-L1) with a combined positive score (CPS) of 10 or more (CPS-10 population), participants whose tumors expressed PD-L1 with a CPS of 1 or more (CPS-1 population), and all the participants. A higher CPS indicates a higher proportion of cells that express PD-L1. RESULTS:A total of 363 participants (234 with a CPS of ≥10 and 347 with a CPS of ≥1) were assigned to the pembrolizumab group and 351 (231 with a CPS of ≥10 and 335 with a CPS of ≥1) to the control group. Surgery was completed in approximately 88% of the participants in each group. At the first interim analysis, the median follow-up was 38.3 months. Event-free survival at 36 months was 59.8% in the pembrolizumab group and 45.9% in the control group (hazard ratio for progression, recurrence, or death, 0.66; 95% confidence interval [CI], 0.49 to 0.88; two-sided P = 0.004) in the CPS-10 population; 58.2% and 44.9%, respectively (hazard ratio, 0.70; 95% CI, 0.55 to 0.89; two-sided P = 0.003), in the CPS-1 population; and 57.6% and 46.4%, respectively (hazard ratio, 0.73; 95% CI, 0.58 to 0.92; two-sided P = 0.008), in the total population. Grade 3 or higher treatment-related adverse events occurred in 44.6% of the participants in the pembrolizumab group and in 42.9% of those in the control group, including death in 1.1% and 0.3%, respectively. Potentially immune-mediated adverse events of grade 3 or higher occurred in 10.0% of the participants in the pembrolizumab group. CONCLUSIONS:The addition of neoadjuvant and adjuvant pembrolizumab to standard care significantly improved event-free survival among participants with locally advanced HNSCC. Neoadjuvant pembrolizumab did not affect the likelihood of surgical completion. No new safety signals were identified. (Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; KEYNOTE-689 ClinicalTrials.gov number, NCT03765918.).

Background Platinum and anti-PD-1 antibodies are the front-line systemic therapy for recurrent or metastatic head and neck squamous cell carcinoma (RM-HNSCC). However, limited data are available on clinical outcomes and appropriate regimens for patients with RM-HNSCC following treatment failure with these agents. Patients and methods We retrospectively analyzed the clinical data of patients with RM-HNSCC from 10 Japanese institutions in whom platinum and nivolumab treatment failed. Results Of the 480 patients included in the study, 236 were treated with the best supportive care and had a median overall survival of 3.1 months. The remaining 244 patients received salvage-line chemotherapy, which was paclitaxel + cetuximab in 72 (30%), paclitaxel or docetaxel in 89 (36%), and tegafur/gimeracil/oteracil in 48 (20%); the respective objective response rates were 54.9%, 27.9%, and 25.5%, with median progression-free survival of 5.4 months and median overall survival of 13.0 months. Multivariable analysis identified disease stabilization or response on prior nivolumab and paclitaxel + cetuximab as salvage-line chemotherapy to be associated with encouraging progression-free and overall survival. Conclusion This study sheds light on clinical outcomes and prognostic factors in patients with RM-HNSCC after failure of platinum and anti-PD-1 antibody therapy. The findings provide essential baseline data for future therapeutic development in salvage-line settings.

Objectives As the global population ages, age-related vocal fold atrophy (ARVA) is increasingly recognized. However, no nationwide epidemiological studies have been conducted. We aimed to investigate the clinical characteristics and treatments of ARVA in Japan, the world’s most aged society. Methods This multicenter retrospective study, part of the Tokyo Voice Center Initiative, analyzed medical records of 1365 patients diagnosed with ARVA between 2018 and 2022. The primary survey examined the involvement of speech language pathologist (SLP) and the routine use of stroboscopic examinations at 34 certified institutions. The secondary survey assessed hoarseness severity (via maximum phonation time and voice handicap index-10), age of onset, treatment methods, and treatment outcomes at 14 certified institutions. Results All diagnoses and assessments were conducted by departments of otolaryngology—head and neck surgery. Of the 1365 patients (637 females, 728 males; mean age: 64.6 ± 14.7 years), 1097 received treatment and 268 did not. Treatments included voice therapy (n = 1031), injection augmentation (n = 162), and surgery (n = 18), with some receiving multiple therapies. Voice therapy was more effective when provided by voice-specialized SLPs. Invasive treatments yielded greater voice improvement overall. Significant differences in age and sex ratios were found between institutions (P < 0.01). Conclusion These findings underscore the need for cross-specialty education, broader awareness of ARVA, and establishment of a national database and severity classification system.

National health insurance coverage for third-generation heat and moisture exchanger (HME) was approved in Japan for patients after total laryngectomy (TL). Our study evaluated the cost-effectiveness of third-generation HMEs (Provox® Life™ such as Provox® Life Night, Go, Home, Energy, and Protect) versus second-generation HMEs and no HME for patients who underwent TL in Japan. A Markov model with five health states was developed using an existing model from a Japanese public healthcare payer perspective, with a time horizon of 10 years and a cycle length of one year. Primary outcome was incremental cost-effectiveness ratio (ICERs), while secondary outcomes were pulmonary infection, mucus plug event and skin irritation. One-way sensitivity analyses (OWSA) and Probabilistic Sensitivity Analysis (PSA) were also conducted to determine the robustness of model conclusions. Third-generation HMEs resulted in an ICER of JPY 2,350,010 per QALY gained, at a willingness-to-pay threshold of JPY 5,000,000 per QALY gained, as compared to second-generation HMEs, indicating cost-effectiveness. Similarly, with an ICER of JPY 4,708,917 per QALY gained, third-generation HMEs were also more cost-effective than no HME. Third-generation HMEs showed a decrease in pulmonary infections (average amounts of pulmonary infections per patient over 10 years: 0.26 vs. 0.39 and 0.55), mucus plug event (0.29 vs. 0.47 and 2.14) and skin irritation (1.80 vs. 2.78 and 0.00) compared to second-generation HMEs and no HME. According to OWSA, the transition probabilities between health states were the main drivers for the cost difference between third-generation and second-generation HMEs. PSA confirmed the robustness of the findings. This is the first study to evaluate cost-effectiveness of HMEs in Japan, suggesting that third-generation HMEs (Provox® Life™) are more cost-effective compared to second-generation HMEs and no HME for patients who underwent TL in Japan.

BACKGROUND:In patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN), the correlation between hematological markers and treatment outcomes has been established. However, their predictive role in the development of immune-related adverse events (irAEs) remains unclear. METHODS:We conducted a multicenter retrospective cohort study to evaluate whether pre-treatment hematological markers-including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and the CRP-albumin-lymphocyte (CALLY) index-predict the development of irAEs in 147 patients with R/M SCCHN treated with pembrolizumab. RESULTS:Lower NLR and PLR, as well as higher LMR and CALLY index, were significantly associated with a higher incidence of irAEs. Furthermore, NLR and LMR were significantly correlated with the occurrence of severe (Grade ≥ 3) irAEs. CONCLUSION:Pre-treatment NLR, PLR, LMR, and CALLY index may serve as useful predictive markers for the development of irAEs in patients with R/M SCCHN treated with pembrolizumab.

Background: Head and neck mucosal melanoma (HNMM) is a rare melanoma. Surgery and radiotherapy (RT) are commonly used; however, their effectiveness remains unclear. In addition, the role of immune checkpoint inhibitors (ICIs) in improving survival in patients with locally advanced HNMM has not been fully evaluated. Patients and methods: This multi-institutional retrospective cohort study analyzed patients with locally advanced HNMM who were treated within the period October 2014 to March 2022. Patients either underwent surgery (S cohort) or received RT (RT cohort). Progression-free survival (PFS) and overall survival (OS) were compared between the S and RT cohorts and between those with and without ICI using propensity score-adjusted models. Results: A total of 304 patients were enrolled: 152 in the S cohort and 152 in the RT cohort. After matching, no significant differences in PFS and OS were observed between the S and RT cohorts. The addition of ICI was associated with significantly improved PFS (hazard ratio 0.50, 95 % confidence interval 0.32-0.80), with a favorable but nonsignificant trend in OS. Subgroup analysis showed that ICI was associated with prolonged OS in the S cohort but had no statistically significant effect in the RT cohort. Disease progression was predominantly distant, irrespective of treatment modality. Conclusion: Surgery and RT were associated with comparable survival outcomes for locally advanced HNMM. ICI was associated with improved PFS, but its relationship with OS needs further investigation. Prospective and randomized studies are needed to refine treatment approaches for this rare malignancy.

OBJECTIVES:To investigate the long-term disease status, clinical course, laryngeal distribution, management, and postoperative recurrence of recurrent respiratory papillomatosis (RRP) diagnosed before the first nationwide survey in Japan. METHODS:As described in our previous report, we conducted a questionnaire-based survey targeting 782 institutions, asking about the presence of RRP patients during the survey period in 2018 and 2019. A detailed questionnaire was subsequently sent to the 196 institutions that reported having at least one patient, inquiring about age, sex, history of recent surgery, Derkay's score, surgical procedures, and postoperative recurrence. The present study analyzed data from patients who had been diagnosed prior to the beginning of the survey period. RESULTS:Data on 318 previously diagnosed patients were collected from 90 institutions. At their first follow-up visit during the survey period, 85 patients (26.7%) had a Derkay's anatomical score of 0. The true vocal folds were the most commonly affected laryngeal subsites. Of the 318 patients, 165 underwent surgery after the first follow-up visit, and recurrence occurred in 106 after this surgery. The 6- and 12-month additional surgery-free rates were 58.9% and 31.8%. These rates were significantly higher in patients who had undergone one or no surgery within a year prior to the first follow-up visit during the survey period than in those who had undergone two or more surgeries (p = 0.01). CONCLUSION:The present study revealed real-world data suggesting that the number of recent surgeries and Derkay's anatomical score may be associated with the clinical course of previously diagnosed RRP. LEVEL OF EVIDENCE: 4:

Advances in narrowband imaging (NBI) have revealed that squamous epithelial lesions form alongside changes in squamous epithelial cells and intrapapillary capillary loops (IPCLs) in the head and neck. However, the molecular interactions between squamous epithelial cells and endothelial cells (ECs) that promote IPCL proliferation are unclear. This study aimed to identify the mechanisms of cooperation between parenchymal squamous cells and stromal IPCLs during the formation of head and neck squamous cell carcinoma (SCC). We investigated ligand-receptor interactions between squamous epithelial and endothelial cells of IPCLs using Visium analysis on frozen, formalin-fixed and paraffin-embedded (FFPE) tissues from hypopharyngeal squamous epithelial lesions. We examined the protein expression in hypopharyngeal superficial squamous epithelial lesions using immunohistochemistry and immunofluorescence. mRNA expression levels of these genes in SCC and non-tumor tissues were analyzed using RT-qPCR. Phenotypic changes were analyzed by inducing candidate genes into SCC cell lines via a lentivirus system. Visium analysis revealed that Fibronectin 1 (FN1) acted as a ligand in endothelial cells, Cellular communication network factor 1 (CCN1) as a ligand in SCC cells, and Integrin subunit alpha V (ITGAV) as a receptor for both FN1 and CCN1. The expression of these three candidates increased in low-grade dysplasia, an early stage of neoplastic lesions, and was significantly higher in invasive SCCs, except for CCN1. When ITGAV was introduced into SCC cell lines (FaDu and Detroit 562) and HaCaT cells treated with FN1, the cells showed increased proliferation ability. SCC develops via ligand-receptor molecular interactions between squamous epithelial and vascular endothelial cells in IPCLs.

The prognosis for T2N0 glottic squamous cell carcinoma (SCC) is generally favorable, with a 5-year overall survival rate of 79%-96% achieved with radiotherapy (RT), the standard nonsurgical treatment for this condition. However, the local control rate for T2N0 glottic SCC treated with RT remains suboptimal, with a 5-year local control rate of only 65%-80%. Local residual disease or recurrence following RT for T2N0 glottic SCC often leads to difficulties in laryngeal preservation. When total laryngectomy is performed as a salvage surgery in such cases, patients lose their physiological ability to speak. Therefore, improving local control and laryngeal preservation rates through RT could substantially improve the quality of life of these patients. Attempts have been made to combine cytotoxic anticancer agents with RT to achieve better local control in patients with T2N0 glottic SCC. In Japan, several studies have evaluated the effects of combining S-1, an oral fluorinated pyrimidine, with RT in these patients. This review highlights the importance of adding chemotherapy to RT in the treatment of patients with T2N0 glottic SCC.

Background: The transseptal approach is widely used in a range of cases in endoscopic transsphenoidal neurosurgery. However, dissecting the mucosa from the septum can lead to perforation in some cases, and the resultant postoperative mucosal perforation can cause symptoms of discomfort, such as recurrent epistaxis, nasal crusting, headache, and nasal obstruction. In this study, we analyzed a technique for preserving the nasal septal cartilage to reduce nasal septal mucosal perforation in terms of the size and frequency of the perforations as well as the symptoms caused by them. We also evaluated the technical complexity of this technique and its potential to cause obstruction of vision and manipulation. Materials and methods: We enrolled a consecutive series of patients who underwent endoscopic transsphenoidal surgery using the nasal septal cartilage-preserving technique. Intraoperative and postoperative mucosal perforations of the nasal septum were confirmed. Results: Eighteen patients underwent surgery using this technique. Surgery was previously performed in only one patient with a pituitary neuroendocrine tumor. Among the other 17 patients who underwent primary surgery, seven showed intraoperative perforation of some size during detachment of the nasal septal mucosa from the nasal septum. Three cases, including a reoperation case, showed nasal septal perforation on outpatient examination a few months later, and no symptoms were associated with postoperative perforation in these three patients. Conclusion: Preserving the septal cartilage prevents perforation of the anterior component of the nasal septum and contributes to reducing the risk of postoperative perforation and its symptomatic occurrence without obstructing intraoperative manipulation.

Neoadjuvant and adjuvant immune checkpoint inhibitors added to SOC (surgery + postoperative radiotherapy [PORT] ± concurrent chemotherapy) yielded promising efficacy results in participants (pts) with LA HNSCC in early phase studies. The randomized, open-label, phase 3 KEYNOTE-689 study (NCT03765918) evaluates neoadjuvant and adjuvant pembrolizumab + SOC vs SOC in this population. Adults with newly diagnosed resectable LA HNSCC (larynx/hypopharynx/oral cavity stage III/IVA; oropharyngeal stage III/IVA p16− or stage III T4 N0-2 p16+) were randomized 1:1 to 2 cycles neoadjuvant and 3 cycles concurrent (during PORT) and 12 cycles adjuvant pembrolizumab 200 mg IV Q3W + SOC vs SOC. SOC included surgery for all pts + PORT 60 Gy in 30 fractions for low-risk, PORT 66 Gy in 33 fractions + 3 cycles concurrent cisplatin 100 mg/m2 Q3W for high-risk, and PORT 70 Gy in 35 fractions + cisplatin for gross residual disease. The primary endpoint is event-free survival (EFS) per RECIST 1.1 by blinded independent central review. Key secondary endpoints are major pathological response (mPR; ≤10% invasive SCC) by blinded independent pathologist review and overall survival (OS). Efficacy endpoints are sequentially assessed in 3 populations: pts with tumors with PD-L1 combined positive score (CPS) ≥10, CPS ≥1, and all pts. Treatment-related adverse events (TRAEs) are graded per CTCAE v4.03. From December 2018 to October 2023, 363 pts were randomized to pembrolizumab + SOC and 351 to SOC. As of 25 July 2024 (first interim analysis), median follow-up was 38.3 months (range, 9.0-66.5). Baseline demographics were balanced between arms. The CPS ≥10 population included 234 pts in the pembrolizumab + SOC arm and 231 in the SOC arm; the CPS ≥1 population included 347 and 335 pts, respectively. EFS (CPS ≥10: median 59.7 vs 26.9 months, HR 0.66, 95% CI 0.49-0.88, P=.00217; CPS ≥1: 59.7 vs 29.6 months, HR 0.70, 95% CI 0.55-0.89, P=.00140; all pts: 51.8 vs 30.4 months, HR 0.73, 95% CI 0.58-0.92, P=.00411) and mPR rate difference (CPS ≥10: 13.7%, 95% CI 9.7-18.7, P<.00001; CPS ≥1: 9.8%, 95% CI 7.0-13.3, P<.00001; all pts: 9.3%, 95% CI 6.7-12.8, P<.00001) analyses were statistically significant with pembrolizumab + SOC vs SOC in all prespecified populations. Additional follow-up for OS is ongoing. Grade ≥3 TRAE frequency was similar (44.6% with pembrolizumab + SOC vs 42.9% with SOC); 4 and 1 deaths occurred due to TRAE, respectively. Immune-mediated AEs occurred in 43.2% of pts with pembrolizumab + SOC, most commonly hypothyroidism (24.7%). Adding neoadjuvant and adjuvant pembrolizumab to SOC significantly improved EFS and mPR rate difference in pts with resectable LA HNSCC independent of CPS. The safety profile of pembrolizumab was consistent with expectations. Ravindra Uppaluri, Robert I. Haddad, Yungan Tao, Christophe Le Tourneau, Nancy Y. Lee, William Westra, Rebecca Chernock, Makoto Tahara, Kevin Harrington, Arkadiy L. Klochikhin, Irene Braña, Gustavo Vasconcelos Alves, Brett G.M. Hughes, Marc Oliva, Iane Pinto Figueiredo Lima, Tsutomu Ueda, Tomasz Rutkowski, Ursula Schroeder, Paul-Stefan Mauz, Thorsten Fuereder, Simon Laban, Nobuhiko Oridate, Aron Popovtzer, Nicolas Mach, Yevhen Korobko, Diogo Alpuim Costa, Anupama Hooda-Nehra, Cristina P. Rodriguez, R. Bryan Bell, Cole Manschot, Kimberly Benjamin, Burak Gumuscu, Douglas Adkins. Neoadjuvant and adjuvant pembrolizumab plus standard of care (SOC) in resectable locally advanced head and neck squamous cell carcinoma (LA HNSCC): Phase 3 KEYNOTE-689 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT001.