Aortic rupture following acute aortitis in a patient with head and neck carcinoma treated with nivolumab: a rare but severe immune-related adverse event.

INTRODUCTION: Immune-related adverse events (irAEs) due to immune checkpoint inhibitors may lead to discontinuation and treatment-related death. Acute aortitis is a rare but severe irAE. CASE PRESENTATION: A 67-year-old man with recurrent lower gingival carcinoma received nivolumab therapy. Twenty-three months later, he experienced chest compression, which resulted in syncope. Following a whole-body computed tomography (CT) scanning, which revealed diffuse thickening of the aorta, and systemic assessments of the causes of aortitis, he was diagnosed with acute aortitis due to irAE. Nivolumab discontinuation and oral steroids improved CT findings. However, 11 months after nivolumab discontinuation, he developed an aortic aneurysmal rupture. Endovascular aortic repair rescued him. A durable anti-cancer response was still observed 4 months after the aortic rupture. CONCLUSION: Although severe irAE, such as acute aortitis, occurred, the patient may still achieve a durable response. A broad examination and prompt treatment of irAE can help improve the patient's survival.

Near-Infrared Autofluorescence Identification of Ectopic Parathyroid Lesions.

Ectopic parathyroid lesions can be difficult to detect. In the present study, we used near-infrared autofluorescence imaging (NIFI) in three cases of ectopic parathyroid lesions. Our results suggest that NIFI may be a confirmation tool for parathyroid pathology and an intraoperative navigation tool in vivo and ex vivo. Laryngoscope, 134:496-500, 2024.

Multicenter prospective phase II trial of concurrent chemoradiotherapy with weekly low-dose carboplatin for cisplatin-ineligible patients with advanced head and neck squamous cell carcinoma.

BACKGROUND: The optimal chemotherapy regimen in concurrent chemoradiotherapy (CCRT) for cisplatin-ineligible head and neck squamous cell carcinoma (HNSCC) has not been established. We aimed to evaluate the feasibility, efficacy, and safety of CCRT with weekly low-dose carboplatin for the treatment of advanced HNSCC in patients who are cisplatin-ineligible. METHODS: This prospective phase II study enrolled adult patients (age ≥ 20 years) with HNSCC receiving whole-neck irradiation including bilateral levels II-IV and who were aged (≥ 75-year-old patients with 40 mL/min estimated glomerular filtration rate [eGFR] or better) or had renal dysfunction (< 75-year-old patients with 30-60 mL/min eGFR). Carboplatin was administered weekly (area under the plasma concentration-time curve = 2.0) for up to seven cycles during concurrent radiotherapy (70 Gy/35 Fr). The primary endpoint was the completion rate of CCRT. Secondary endpoints included overall response rate and incidence of adverse events. RESULTS: Among the 30 patients enrolled, 28 were men. The median age was 73.5 years. Seventeen patients were < 75 years whereas 13 were ≥ 75 years old. The completion rate of CCRT was 90%. The overall response rate was 90%. Grade 3 adverse events that occurred in 10% or more patients were oral/pharyngeal mucositis (47%), leukocytopenia (20%), and neutropenia (10%). Grade 4 adverse events occurred in one patient (elevation of alanine aminotransferase level). No treatment-related deaths occurred. CONCLUSION: CCRT with weekly low-dose carboplatin is a promising treatment option, with favorable feasibility, efficacy, and acceptable toxicity, for patients who are cisplatin-ineligible with advanced HNSCC. CLINICAL TRIAL REGISTRATION NUMBER: jRCTs031190028.

Sarcopenia Index Predicts Short-Term Prognosis of Head and Neck Squamous Cell Carcinoma.

The sarcopenia index (SI), calculated as [(serum creatinine/serum cystatin C) × 100], maybe a simpler alternative for measuring muscle mass than computed tomography (CT) and bioelectrical impedance analysis (BIA). We enrolled 112 patients with head and neck cancers (HNC). The correlation of the SI with muscle surface area measured by CT (CTMSA, n = 82) and muscle mass by BIA (BIA-MM, n = 41) was tested. Cutoff values were set for SI, CTMSA, and BIA-MM. Overall survival (OS) was compared between the high- and low-SI/CTMSA/BIA-MM groups. The SI was correlated with CTMSA (r = 0.43) and BIA-MM (r = 0.52). The optimal cutoff values of SI, CTMSA, and BIA-MM were 76.1 (area under the curve [AUC] = 0.67), 129.2 (AUC = 0.59), and 46.1 (AUC = 0.62), respectively. OS was significantly lower in the low-SI group (78% at 1 year and 69% at 2 years) than in the high-SI group (94% at 1 year and 86% at 2 years; p = 0.006). There was no significant difference in OS between the low-and high-CTMSA and -BIA-MM groups. The SI, which only requires a blood sample, is a useful marker of muscle mass that correlates with short-term prognosis in patients with HNC.

Role of eosinophilia in patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab: Prediction of immune-related adverse events and favorable outcome.

INTRODUCTION: Immune-related adverse events (irAEs) are prognostic factors for patients on nivolumab. However, predictors of irAEs have not yet been identified. We aimed to investigate the predictors of irAEs occurrence and nivolumab discontinuation due to irAEs. METHODS: Sixty-two patients with recurrent/metastatic head and neck squamous cell carcinoma received nivolumab therapy between June 2017 and December 2020. Treatment outcome was compared between the groups with or without irAEs. The irAE (+) group was further divided by nivolumab discontinuation. Progression-free survival (PFS) and overall survival (OS) were compared between the groups. Predictors of irAE occurrence were analyzed. RESULTS: Twenty-one patients (33.9%) developed irAEs, and six (28.6%) discontinued nivolumab due to severe irAEs. The irAE (+) group had significantly longer PFS and OS than the irAE (-) group (median PFS, 12.7 vs. 1.9 months; median OS, 33.1 vs. 12.8 months). The treatment outcomes in the discontinuation group were comparable to those in the non-discontinuation group. The maximum absolute eosinophil count (AEC) during nivolumab therapy was significantly higher in the irAE (+) group than in the irAE (-) group (548.8 vs. 182) and higher in the discontinuation group than in the non-discontinuation group (729.3 vs. 368.6). The receiver operating characteristic curve showed that the maximum AEC had a moderate-to-high accuracy for predicting irAE occurrence (area under the curve [AUC], 0.757) and nivolumab discontinuation (AUC, 0.893). DISCUSSION: Monitoring AEC during nivolumab therapy may be useful in predicting irAE occurrence, nivolumab discontinuation, and disease prognosis.

Treatment Outcome in Head and Neck Cancer With Distant Metastasis at Initial Diagnosis.

OBJECTIVE: Recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) treatment has changed dramatically with the introduction of immune checkpoint inhibitors (ICIs). However, there are few reports of treatment outcomes on HNSCC with distant metastasis (M1) at initial diagnosis, and its treatment strategy has not been standardized. We aimed to analyze the treatment outcome and prognostic factors of patients with HNSCC with initial M1 disease. METHODS: In this multi-institutional retrospective study, 98 patients with HNSCC were initially diagnosed with M1 disease between 2007 and 2021. The patients were divided into the non-palliative (received any systemic chemotherapy, n = 60) and palliative (did not receive systemic chemotherapy, n = 38) groups. Overall survival (OS) was compared between the groups. In the non-palliative group, predictors of OS were explored based on patient characteristics and treatment details. RESULTS: The median OS in the non-palliative group was 15 months (95% confidence interval [CI], 10-20), which was significantly longer than that in the palliative group (3 months, 95% CI, 2-5) (p < 0.001). Multivariate analysis revealed that administration of locoregional radiation therapy (RT) (hazard ratio [HR] 0.407 [95% CI 0.197-0.844]; p = 0.016), ICIs (HR 0.216 [95% CI 0.088-0.532]; p < 0.001) and RT/surgery for distant metastasis (HR 0.373 [95% CI 0.150-0.932]; p = 0.034) were the independent prognostic factors of OS. CONCLUSION: An intensive treatment strategy combining systemic therapy using ICIs with RT/surgery for locoregional or distant metastasis may yield a survival benefit for patients with HNSCC with M1 disease. LEVEL OF EVIDENCE: 4 Laryngoscope, 2023.

Distribution patterns of infraorbital nerve branches and risk for injury.

BACKGROUND: During oral and head and neck surgery, oral vestibular incisions may require a transverse incision on the upper lip mucosa, resulting in possible sensory disturbances in the area innervated by infraorbital nerve (ION) branches. Although sensory disturbances are attributed to nerve injuries, anatomy textbooks have not showed the precise distribution patterns of the ION branches in the upper lip. Furthermore, no detailed study has been available on this issue. This study aimed to reveal the precise distribution patterns of ION branches in the upper lip by dissecting the detached upper lip and cheek area using a stereomicroscope. METHODS: During a gross anatomy course at Niigata University (2021-2022), nine human cadavers were examined with special focus on the relationship between ION branches in the upper lip and the layered structure of facial muscles. RESULTS: The ION branched to the inferior palpebral (IP), external and internal nasal, and superior labial (lateral and medial) nerves. The ION branches in the upper lip did not run in a horizontal pattern from outside to inside but showed a predominantly vertical pattern. Considering their course, incising the upper lip mucosa transversely may cause paresthesia of the ION branches. The internal nasal (IN) and medial superior labial (SLm) branches tended to penetrate the orbicularis oris and descend between this muscle and labial glands, whereas the lateral superior labial (SLl) branches tended to innervate the skin. CONCLUSIONS: These findings suggest that a lateral mucosal incision is recommended for oral vestibular incisions of the upper lip and that deeper incisions to the labial glands should be avoided when incising the medial side to preserve the ION during surgery from an anatomical point of view.

Head and neck small-cell carcinoma: A multicenter study of 39 cases from 10 institutions.

Objective: Basal information of head and neck small-cell carcinoma (HNSmCC) including epidemiology, primary site, treatment, and prognosis remains sparse due to its rarity. We report here a multicenter retrospective study on the diagnosis, treatment, and outcomes of patients with HNSmCC. Materials and methods: This study involved 47 patients with HNSmCC from 10 participating institutions. Eight patients were excluded for whom no pathological specimens were available (n = 2) and for discrepant central pathological judgements (n = 6). The remaining 39 patients were processed for data analysis. Results: As pretreatment examinations, computed tomography (CT) was performed for the brain (n = 8), neck (n = 39), and chest (n = 32), magnetic resonance imaging (MRI) for the brain (n = 4) and neck (n = 23), positron emission tomography-CT (PET-CT) in 23 patients, bone scintigraphy in 4, neck ultrasonography in 9, and tumor markers in 25. Primary sites were oral cavity (n = 1), nasal cavity/paranasal sinuses (n = 16), nasopharynx (n = 2), oropharynx (n = 4), hypopharynx (n = 2), larynx (n = 6), salivary gland (n = 3), thyroid (n = 2), and others (n = 3). Stages were II/III/IV-A/IV-B/IV-C/Not determined = 3/5/16/6/5/4; stage IV comprised 69%. No patient had brain metastases. First-line treatments were divided into 3 groups: the chemoradiotherapy (CRT) group (n = 27), non-CRT group (n = 8), and best supportive care group (n = 4). The CRT group included concurrent CRT (CCRT) (n = 17), chemotherapy (Chemo) followed by radiotherapy (RT) (n = 5), and surgery (Surg) followed by CCRT (n = 5). The non-CRT group included Surg followed by RT (n = 2), Surg followed by Chemo (n = 1), RT alone (n = 2), and Chemo alone (n = 3). The 1-year/2-year overall survival (OS) of all 39 patients was 65.3/53.3%. The 1-year OS of the CRT group (77.6%) was significantly better compared with the non-CRT group (31.3%). There were no significant differences in adverse events between the CCRT group (n = 22) and the Chemo without concurrent RT group (n = 9). Conclusion: Neck and chest CT, neck MRI, and PET-CT would be necessary and sufficient examinations in the diagnostic set up for HNSmCC. CCRT may be recommended as the first-line treatment. The 1-year/2-year OS was 65.3%/53.3%. This study would provide basal data for a proposing the diagnostic and treatment algorithms for HNSmCC.

Identification of novel prognostic and predictive biomarkers in salivary duct carcinoma via comprehensive molecular profiling.

Molecular targets and predictive biomarkers for prognosis in salivary duct carcinoma (SDC) have not been fully identified. We conducted comprehensive molecular profiling to discover novel biomarkers for SDC. A total of 67 SDC samples were examined with DNA sequencing of 464 genes and transcriptome analysis in combination with the clinicopathological characteristics of the individuals. Prognostic biomarkers associated with response to combined androgen blockade (CAB) treatment were explored using mRNA expression data from 27 cases. Oncogenic mutations in receptor tyrosine kinase (RTK) genes or genes in the MAPK pathway were identified in 55 cases (82.1%). Alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway were identified in 38 cases (56.7%). Interestingly, patient prognosis could be predicted using mRNA expression profiles, but not genetic mutation profiles. The risk score generated from the expression data of a four-gene set that includes the ADAMTS1, DSC1, RNF39, and IGLL5 genes was a significant prognostic marker for overall survival in the cohort (HR = 5.99, 95% confidence interval (CI) = 2.73-13.1, p = 7.8 × 10-6). Another risk score constructed from the expression of CD3E and LDB3 was a strong prognostic marker for progression-free survival for CAB treatment (p = 0.03). Mutations in RTK genes, MAPK pathway genes, and PI3K/AKT pathway genes likely represent key mutations in SDC tumorigenesis. The gene expression profiles identified in this study may be useful for stratifying patients who are good candidates for CAB treatment and may benefit from additional systemic therapies.

Survival benefit of HER2-targeted or androgen deprivation therapy in salivary duct carcinoma.

Background: The efficacy and safety of human epidermal growth factor receptor 2 (HER2)-targeted therapy and androgen deprivation therapy (ADT) for locally advanced or recurrent or metastatic (LA/RM) salivary duct carcinoma (SDC) have been reported in prospective studies. However, the survival benefit of these therapies to conventional therapy remains controversial, and whether HER2-targeted therapy or ADT should be chosen in HER2- and androgen receptor (AR)-positive SDC patients remains unknown. Methods: Overall, 323 LA/RM SDC patients treated at seven institutions between August 1992 and June 2020 were retrospectively enrolled. The primary aim was to analyze the effect of HER2-targeted therapy and ADT on overall survival from the diagnosis of LA/RM disease to death from any cause (OS1). The secondary indicators included the overall response rate (ORR), clinical benefit rate (CBR), overall survival from therapy initiation for LA/RM disease (OS2), progression-free survival (PFS), time to second progression (PFS2), duration of response (DoR), and duration of clinical benefit (DoCB) of HER2-targeted therapy or ADT as first-line therapy for HER2-positive/AR-positive SDC. Results: Patients treated with HER2-targeted therapy or ADT had longer OS1 than those treated without these therapies (Median OS1: historical control, 21.6 months; HER2-targeted therapy, 50.6 months; ADT, 32.8 months; HER2-targeted therapy followed by ADT, 42.4 months; and ADT followed by HER2-targeted therapy, 45.2 months, p < 0.001). Among HER2-positive/AR-positive SDC patients, although HER2-targeted therapy had better ORR, CBR, and PFS than those of ADT as first-line therapy, we found no significant differences between HER2-targeted therapy and ADT regarding OS2, PFS2, DoR, and DoCB. Conclusion: Patients treated with HER2-targeted therapy and ADT showed longer survival in LA/RM SDC. HER2-targeted therapy can be recommended prior to ADT for HER2-positive/AR-positive SDC. It is warranted to establish a biomarker that could predict the efficacy of clinical benefit or better response in ADT.

Actual prevalence of hypoparathyroidism after total thyroidectomy: a health insurance claims-database study.

PURPOSE: Persistent hypoparathyroidism (hypoPT) is a major complication of total thyroidectomy. Nonetheless, previous reports may have underestimated the prevalence of hypoPT due to patient selection bias. We aimed to estimate the actual prevalence of persistent hypoPT after total thyroidectomy and to find predictive factors for postoperative hypoPT. METHODS: This study retrospectively reviewed data from a health insurance claims-based database provided by the Japan Medical Data Center Co., Ltd. From 2009 to 2019, 2388 patients who underwent total thyroidectomy were identified using the medical procedure codes. Persistent hypoPT was defined as the prescription of active vitamin D supplements for >1 year postoperatively and the assignment of hypoPT codes. The prevalence of persistent hypoPT was estimated at two different levels: minimum and maximum estimations with or without postoperative osteoporosis and/or renal failure codes. Correlates for persistent hypoPT were investigated among several demographic and clinical variables. RESULTS: Of the 2388 patients, 1752 (73.4%) were women with a mean age of 45 years. The types of diseases were: benign thyroid disease (n = 235), malignant thyroid tumors (n = 1570), Graves ' disease (n = 558), and malignancy combined with Graves' disease (n = 25). The minimum and the maximum estimation of the prevalence of persistent hypoPT were 15.0 and 20.3%, respectively. Multivariate logistic regression analysis showed that the malignant tumor (odds ratio, 1.8) independently correlated with persistent hypoPT. CONCLUSIONS: The prevalence of persistent hypoPT after total thyroidectomy estimated by the claims-based database was higher than previously recognized. Comprehensive attempts to preserve parathyroid function, especially in malignant diseases, are essential.

Head and neck cancer fungating wounds: a novel odour transferrer.

OBJECTIVE: The management for malodour of malignant fungating wounds (MFWs) in head and neck cancer (HNC) is unestablished. We evaluated the effects of a novel odour transferrer on malodour generated by MFWs in patients with HNC. METHODS: A spray-type odour transferrer approved by the Japanese government for safe use in humans produces a good scent by binding to bad odour. The odour of MFWs in 13 patients with HNC was scored by 37 medical staff and the patients' families using an odour scale ranging from 0 to 4 before and 1 week after application of the odour transferrer. RESULTS: The odour score marked by all investigators (n=37), nurses (n=21) and doctors (n=11) decreased significantly (p<0.01). The odour score decreased by more than 2 points for 73% of all investigators after odour transferrer application. CONCLUSION: This novel odour transferrer functions as an effective deodorant for MFWs in patients with HNC. It can be used by non-medical staff and may benefit patients with bad odours arising from MFWs as well as their families and medical staff.

Treatment outcomes of mucosal melanoma of head and neck: Efficacy of immune checkpoint inhibitors for advanced disease.

Background: Head and neck mucosal melanoma (HNMM) is a rare and aggressive subtype of melanoma. HNMM often develops as a recurrent or metastatic disease, and its prognosis is worse than that of cutaneous melanoma. Recent large-scale clinical studies have reported favorable outcomes with immune checkpoint inhibitors (ICIs) for melanoma. However, these clinical trials included only a small number of HNMM cases. This study aimed to estimate treatment outcomes and prognostic predictors of ICIs for advanced HNMM. Methods: Cases of advanced HNMM, defined as unresectable or metastatic HNMM at the initial diagnosis (five patients) or development of recurrent/metastatic HNMM after initial treatment (27 patients), were included in this study. Survival analysis and a search for prognostic factors were performed for these 32 patients. Furthermore, the detailed clinical course of patients who received ICI treatment was investigated. Results: The median overall survival (OS) of 32 patients with advanced HNMM was 25.3 months. The estimated 1-, 3-, and 5-year OS rates were 68.4%, 42.8%, and 34.3%, respectively. Fourteen patients (43.7%) received ICIs, whereas 18 (56.3%) did not. Univariate analysis showed that ICI treatment was the only factor associated with a better 1-year OS. Patients who received ICI treatment had significantly longer OS (median OS: not reached, 1-year OS: 85.7%) than those who did not (median OS: 11.3 months, 1-year OS: 54.5%). The overall response and disease control rates of patients who received ICI treatment were 50% and 64.3%, respectively. Patients who achieved complete response (CR) or partial response (PR) to ICI treatment survived significantly longer (1-year OS: 100%) than those who did not (1-year OS: 71.4%). Among the five patients who discontinued ICI treatment due to severe immune-related adverse events (irAEs), four did not receive salvage treatments but showed durable treatment effects and survived for 9.8-54.2 months at the end of the follow-up period. Conclusions: ICI treatment achieved a favorable OS for advanced HNMM. CR/PR to ICI treatment and discontinuation owing to severe irAEs were favorable predictors of OS.

Chemoradiotherapy with 3-weekly CDDP 80†mg/m2 for head and neck squamous cell carcinoma: 5-year survival data from a phase 2 study.

Objective: The global standard for chemoradiation therapy (CCRT) for head and neck squamous cell carcinoma is cisplatin 100 mg/m2 administered once every three weeks, although cisplatin 80 mg/m2 is also widely used as an alternative treatment to reduce adverse events in Japan. We aimed to assess the long-term survival outcomes and late adverse events associated with CCRT with a 3-weekly cisplatin dose of 80 mg/m2. Methods: A phase 2 study on CCRT with a 3-weekly cisplatin dose of 80 mg/m2 was performed in 47 patients between April 2015 and December 2016 at four centers in Japan. Survival outcomes and late adverse events at 5 years after this phase 2 trial were investigated. Results: The median follow-up period was 61 months. The 5-year progression-free survival/overall survival of all 47 patients was 66.0%/76.6%, while that of patients with stage III, IV disease (UICC) was 65.6%/71.9%. Seventeen patients (36%) experienced dysphagia as a late adverse event. Univariate and multivariate analyses revealed a significant association between acute mucositis/low body mass index (BMI) during CCRT and late dysphagia. Conclusion: The survival outcomes of CCRT with a 3-weekly cisplatin dose of 80 mg/m2 may be comparable to the previously reported dose of 100 mg/m2. Acute mucositis and low BMI at CCRT were risk factors for late dysphagia, indicating the importance of managing these conditions during CCRT to prevent late adverse events. Caution and care for acute mucositis and swallowing training in patients with low BMI may be important for preventing late-stage dysphagia.

Carotid blowout-a rare but fatal complication of endoscopic submucosal dissection of superficial hypopharyngeal carcinoma after radiotherapy.

Endoscopic submucosal dissection (ESD) has gained wide acceptance as a minimally invasive and curative surgery for superficial head and neck carcinoma. However, the safety of ESD for superficial pharyngeal carcinoma after radiotherapy has not been elucidated. Superficial hypopharyngeal carcinoma of the left pyriform sinus developed in a 76-year-old man who had undergone concurrent chemoradiotherapy for T2N2bM0 pyriform sinus carcinoma on the opposite side 12 months before. He underwent ESD without complications. Because tumor invasion into the muscular layer was a concern, the muscular layer was partially resected with the tumor. Twelve days after discharge, he presented with a sore throat and difficulty in swallowing. Endoscopy and computed tomography revealed necrosis due to wound infection with abscess formation around the left carotid artery. The common carotid artery subsequently ruptured. Although the surgical intervention was performed, he passed away 46 days after ESD due to carotid blowout. ESD is a minimally invasive treatment for superficial head and neck carcinoma, but carotid blowout can occur in cases after radiation. Prior radiotherapy and deeper dissection into the muscular layer may hamper wound epithelization, resulting in infection-induced necrosis and carotid blowout. Diligent monitoring of wound healing is essential in patients who have previously undergone irradiation.

Treatment Outcomes and the Safety of Chemoradiotherapy With High-Dose CDDP for Elderly Patients With Head and Neck Squamous Cell Carcinoma: A Propensity Score Matching Study.

Objective: We aimed to compare the outcomes and safety of chemoradiotherapy (CRT) between elderly and non-elderly patients with head and neck squamous cell carcinoma (HNSCC). It is difficult to assess the causal effect of age because of possible differences in general conditions among individuals. Therefore, we adjusted the background factors of elderly and non-elderly patients using propensity score matching (PSM). Methods: A total of 146 patients with HNSCC who received CRT were divided into an elderly (≥70 years, n = 35) and non-elderly group (<70 years, n = 111). Pre-treatment characteristics, including the performance status, Charlson comorbidity index, body mass index, primary site, and TNM stage were adjusted by PSM. We compared the outcomes and safety of CRT with high-dose single-agent cisplatin (CDDP) as well as outcomes following recurrence between the groups, before and after PSM. Results: The total dose of CDDP administered during CRT was significantly lower in the elderly group before PSM. However, it became comparable to the non-elderly group and adverse events did not differ between the groups following PSM, resulting in a comparable CRT completion rate. Overall-, disease specific-, and progression-free survivals of elderly patients were comparable to those of non-elderly patients following PSM. In contrast, elderly patients with recurrence could receive fewer salvage treatments than their non-elderly counterparts, resulting in worse survival. Conclusions: CRT with high-dose CDDP is safe and effective for the treatment of elderly patients with HNSCC. However, salvage treatments can be rarely conducted for elderly patients with a recurrence, considering a deterioration of their general condition.

Treatment Outcome of External Auditory Canal Carcinoma: The Utility of Lateral Temporal Bone Resection.

We examined the role of lateral temporal bone resection (LTBR) in the treatment of external ear canal (EAC) carcinoma between 2007 and 2018. The estimated 3-year disease-free survival (DFS) and disease-specific survival (DSS) according to the tumor stage and treatments were investigated in 36 patients with EAC squamous cell carcinoma. T stage classification according to the University of Pittsburgh staging system was as follows: 14 patients in T1, four patients in T2, nine patients in T3, and nine patients in T4. The 3-year DFS rate was 77.4% for T1 tumors, 100% for T2, 44.4% for T3 tumors, and 11.1% for T4 tumors (p < 001). The 3-year DSS rate was 100% for T1/T2 tumors, 87.5% for T3 tumors, and 11.1% for T4 tumors (p < 0.01). T1/T2 patients received mostly LTBR. Among nine T3 tumors, five patients (56%) received LTBR combined with preoperative chemotherapy and/or postoperative radiation (RT). Four of them had negative surgical margin and survived with no evidence of disease. The DFS of T3 patients who underwent concurrent chemoradiotherapy and LTBR was 0 and 80%, respectively (p = 0.048). For T1/T2 tumors, surgery achieved an excellent outcome. For T3 tumors, LTBR achieved negative surgical margin and showed good survival when combined with preoperative chemotherapy and/or postoperative RT. In contrast, the prognosis of T3 patients who could not undergo surgery was as poor as that of T4 patients. Therefore, in addition to subtotal temporal bone resection, LTBR-based treatment strategy may be a treatment option for limited cases of T3 patients.

The Role of the EZH2 and H3K27me3 Expression as a Predictor of Clinical Outcomes in Salivary Duct Carcinoma Patients: A Large-Series Study With Emphasis on the Relevance to the Combined Androgen Blockade and HER2-Targeted Therapy.

OBJECTIVE: Salivary duct carcinoma (SDC) is a highly aggressive and uncommon tumor arising not only de novo but also in pleomorphic adenoma. Androgen receptor (AR)- and HER2-targeted therapy have recently been introduced for SDC as promising treatment options; however, no predictive biomarkers have yet been established. EZH2 and H3K27me3 are closely linked to the development and progression of various cancers, and EZH2 is also expected to be a desirable therapeutic target. We therefore explored the clinicopathological and prognostic implications of EZH2 and H3K27me3 in a large cohort of SDC patients, focusing on their impact on the therapeutic efficacy of AR- or HER2-targeted therapy. MATERIALS AND METHODS: The EZH2 and H3K27me3 immunohistochemical expression and EZH2 Y646 gain-of-function mutation status were examined in 226 SDCs, and the relationship with the clinicopathological factors as well as clinical outcomes were evaluated within the three groups depending on the treatment: AR-targeted (combined androgen blockade with leuprorelin acetate and bicalutamide; 89 cases), HER2-targeted (trastuzumab and docetaxel; 42 cases), and conventional therapy (112 cases). RESULTS: EZH2 and H3K27me3 were variably immunoreactive in most SDCs. A positive correlation was found between the expression of EZH2 and H3K27me3. The EZH2 expression in the SDC component was significantly higher than that in the pre-existing pleomorphic adenoma component. EZH2 Y646 was not identified in any cases. EZH2-high cases more frequently had an advanced clinical stage and aggressive histological features than EZH2-low cases. An EZH2-high status in patients treated with AR-targeted therapy was associated with a significantly shorter progression-free and overall survival as well as a lower objective response rate and clinical benefit rate. In addition, a H3K27me3-high status in patients treated with AR-targeted therapy was related to a shorter overall survival. Conversely, there was no association between the EZH2 and H3K27me3 expression and the clinical outcomes in the conventional or HER2-targeted therapy groups. CONCLUSIONS: A high expression of EZH2 and H3K27me3 in SDC might be a predictor of a poor efficacy of AR-targeted therapy. Our data provide new insights into the role of EZH2 and H3K27me3 in therapeutic strategies for SDC.