PSMD1 as a prognostic marker and potential target in oropharyngeal cancer.

BACKGROUND: Despite the diverse genetic mutations in head and neck cancer, the chemotherapy outcome for this cancer has not improved for decades. It is urgent to select prognostic factors and therapeutic targets for oropharyngeal cancer to establish precision medicine. Recent studies have identified PSMD1 as a potential prognostic marker in several cancers. We aimed to assess the prognostic significance of PSMD1 expression in oropharyngeal squamous cell carcinoma (OPSCC) patients using immunohistochemistry. METHODS: We studied 64 individuals with OPSCC tissue from surgery at Seoul National University Bundang Hospital between April 2008 and August 2017. Immunostaining analysis was conducted on the tissue microarray (TMA) sections (4 µm) for p16 and PSMD1. H-score, which scale from 0 to 300, was calculated from each nucleus, cytoplasm, and cellular expression. Clinicopathological data were compared with Chi-squared test, Fisher's exact test, t-test, and logistic regression. Survival data until 2021 were achieved from national statistical office of Korea. Kaplan-Meier method and cox-regression model were used for disease-specific survival (DSS) analysis. RESULTS: H-score of 90 in nucleus was appropriate cutoff value for 'High PSMD1 expression' in OPSCC. Tonsil was more frequent location in low PSMD1 group (42/52, 80.8%) than in high PSMD1 group (4/12, 33.3%; P = .002). Early-stage tumor was more frequent in in low PSMD1 group (45/52, 86.5%) than in high PSMD1 group (6/12, 50%; P = .005). HPV was more positive in low PSMD1 group (43/52, 82.7%) than in high PSMD1 group (5/12, 41.7%; P = .016). Patients with PSMD1 high expression showed poorer DSS than in patients with PSMD1 low expression (P = .006 in log rank test). In multivariate analysis, PSMD1 expression, pathologic T staging, and specimen age were found to be associated with DSS (P = .011, P = .025, P = .029, respectively). CONCLUSIONS: In our study, we established PSMD1 as a negative prognostic factor in oropharyngeal squamous cell carcinoma, indicating its potential as a target for targeted therapy and paving the way for future in vitro studies on drug repositioning.

Adjuvant radiotherapy in node-negative salivary malignancies of the parotid gland: A multi-institutional analysis.

BACKGROUND AND PURPOSE: To determine the role of adjuvant radiotherapy (ART) in parotid gland cancer without nodal metastasis, we evaluated the survival outcomes, prognostic factors, and dose-response relationships in patients with node-negative parotid gland cancer patients. MATERIALS AND METHODS: Patients who underwent curative parotidectomy and were pathologically diagnosed with parotid gland cancer without regional or distant metastases between 2004 and 2019 were reviewed. The benefit of ART in terms of locoregional control (LRC) and progression-free survival (PFS) were evaluated. RESULTS: In total, 261 patients were included in the analysis. Of them, 45.2 % received ART. The median follow-up period was 66.8 months. Multivariate analysis revealed that histological grade and ART were independent prognostic factors for LRC and PFS (all p <.05). For patients with high-grade histology, ART was associated with a significant improvement in 5-year LRC (p =.005) and PFS (p =.009). Among patients with high-grade histology who completed RT, higher biologic effective dose (≥77 Gy10) significantly increased PFS (adjusted hazard ratio [HR], 0.10 per 1-Gy increase; 95 % confidence interval [CI], 0.02-0.58; p =.010). ART significantly improved LRC (p =.039) in patients with low-to-intermediate histological grade as well per multivariate analysis, and subgroup analyses revealed patients with T3-4 stage and close/positive resection margins (<1 mm) would benefit from ART. CONCLUSION: ART should be strongly recommended for patients with node-negative parotid gland cancer with high-grade histology in terms of disease control and survival. In patients with low-to-intermediate-grade disease, those with high T stage and incomplete resection margin benefit with ART.

Effect of postoperative radiotherapy for patients with differentiated thyroid cancer.

OBJECTIVE: We evaluated the efficacy and safety of postoperative radiotherapy (PORT) for differentiated thyroid cancer (DTC) with high risk features. MATERIALS AND METHODS: This retrospective study analyzed 187 patients treated for DTC from 1985 to 2019. DTC referred to nonanaplastic thyroid cancer originating from follicular cells. PORT was defined as the administration of external beam radiation to the thyroid and regional lymph nodes following surgery for initially diagnosed DTC. The patients were included in the analysis if they received PORT or exhibited any of the following features: (a) pT4 or pN1b according to the 8th American Joint Committee on Cancer, (b) poorly differentiated thyroid cancer (PDTC), or (c) unfavourable variants such as anaplastic foci and etc. After 1:1 propensity matching, a total of 108 patients were analyzed according to PORT receipt. The median follow-up duration of the matched group was 10.4 years. RESULTS: After matching, most of the variables became balanced, but the PORT group still had more PDTC and DTC with anaplastic foci. Radioactive iodine (RAI) was less frequently administered in the PORT group. PORT yielded a significantly higher 5-year locoregional recurrence free survival (LRFS) than the No PORT group (5-year LRFS 86.1% vs. 72.7%, p = 0.022), but the 10-year cancer specific survival (CSS) was similar between them (97.8% vs. 85.9%, p = 0.122). The multivariable analysis indicated that PORT was a favourable prognostic factor (Hazard ratio 0.3, 95% Confidence interval 0.1-0.8, p = 0.02) for LRFS, but not for CSS. Among 133 patients without PORT for initial disease, 39 of them received salvage surgery followed by salvage PORT. No severe toxicity after PORT was reported. CONCLUSION: PORT reduced locoregional recurrence in DTC patients without severe toxicity. PORT can be an effective and safe treatment to improve locoregional control in DTC with high risk features. However, further study is warranted to identify those who can benefit from PORT.

The Expression of Defensin-Associated Genes May Be Correlated With Lymph Node Metastasis of Early-Stage Tongue Cancer.

OBJECTIVES: We aimed to assess the genetic differences between cases of early-stage tongue cancer that were positive or negative for lymph node metastasis. METHODS: In total, 35 cases of tongue cancer with RNA sequencing data were enrolled in this study. The gene expression profile of the following two groups was compared: N0 group (T stage 1 or 2 with N0 stage) and N+ group (T stage 1 or 2 with N+ stage). Using the R and limma packages in the Bioconductor program, we extracted the differentially expressed genes (DEGs). Gene ontology and pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integration Discovery (DAVID) online tool. Immune cell infiltration was analyzed using the CIBERSORT online program. Immunochemical staining of the cancer tissue was evaluated and The Cancer Genome Atlas (TCGA) data were analyzed to validate the identified DEGs. RESULTS: No significant differences were found in the infiltration of 22 types of immune cells. Among a total of 51 identified DEGs, 14 genes were significantly upregulated, while 37 genes were significantly downregulated (P<0.01; fold change >2). Pathway analysis revealed significant associations with the arachidonic acid metabolism-related pathway, calcium signaling, and the muscle contraction pathway. The following DEGs were the most significantly different between the two groups: DEFB4A, SPRR2B, DEFB103B, SPRR2G, DEFB4B, and FAM25A. TCGA data showed that DEFB4A and DEFB103B were more highly expressed in the N0 group than in the N+ group, although the difference did not achieve statistical significance. Immunochemical staining of cancer tissue revealed significantly higher expression of defensin in the N0 group. CONCLUSION: . Defensin (DEFB4A, DEFB103B, DEFB4B) may be a novel biomarker for early regional metastasis in T1/2 tongue cancer.

Identification of differentially expressed microRNAs as potential biomarkers for carcinoma ex pleomorphic adenoma.

Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignancy that transforms from PA. Early detection of the carcinoma by biopsy is difficult due to similar histopathology of the malignant and benign components. To address this, we investigated and compared the characteristic miRNA expression patterns across samples of the PA, carcinomatous portions (CA) of CXPA, as well as conventional PA. We selected 13 CXPA and 16 conventional PA FFPE samples, separated the PA and CA portions of CXPA samples and conducted miRNA profiling for each group. Among 13 transcripts that were differentially expressed between PA and CA of CXPA, eight miRNAs were up-regulated and five down-regulated in CA. Bioinformatic analysis revealed that the up-regulated miRNAs were related to cancer progression and down-regulated ones to tumor suppression. Additionally, seven miRNAs were significantly up-regulated in PA of CXPA compared to conventional PA, although they are histopathologically similar. Almost all of these transcripts interacted with TP53, a well-known tumor suppressor. In conclusion, we identified differentially expressed miRNAs in PA and CA of CXPA, which were closely associated with TP53 and various cancer-related pathways. We also identified differentially expressed miRNAs in the PA of CXPA and conventional PA which may serve as potential biomarkers.

Effects of ischemic conditioning on head and neck free flap oxygenation: a randomized controlled trial.

Flap failure after microvascular reconstructive surgery is a rare but devastating complication caused by reperfusion injury and tissue hypoperfusion. Remote ischemic conditioning (RIC) provides protection against ischemia/reperfusion injury and reduces tissue infarction. We hypothesized that RIC would enhance flap oxygenation and exert organ-protective effects during head and neck free flap reconstructive surgery. Adult patients undergoing free flap transfer surgery for head and neck cancer were randomized to receive either RIC or sham-RIC during surgery. RIC consisted of four cycles of 5-min ischemia and 5-min reperfusion applied to the upper or lower extremity. The primary endpoint, tissue oxygen saturation of the flap, was measured by near-infrared spectroscopy on the first postoperative day. Organ-protective effects of RIC were evaluated with infarct size of rat hearts perfused with plasma dialysate from patients received RIC or sham-RIC. Between April 2018 and July 2019, 50 patients were randomized (each n = 25) and 46 were analyzed in the RIC (n = 23) or sham-RIC (n = 23) groups. Tissue oxygen saturation of the flap was similar between the groups (85 ± 12% vs 83 ± 9% in the RIC vs sham-RIC groups; P = 0.471). Myocardial infarct size after treatment of plasma dialysate was significantly reduced in the RIC group (44 ± 7% to 26 ± 6%; P = 0.018) compared to the sham-RIC group (42 ± 6% to 37 ± 7%; P = 0.388). RIC did not improve tissue oxygenation of the transferred free flap in head and neck cancer reconstructive surgery. However, there was evidence of organ-protective effects of RIC in experimental models.Trial registration: Registry number of ClinicalTrials.gov: NCT03474952.

Deep learning model for tongue cancer diagnosis using endoscopic images.

In this study, we developed a deep learning model to identify patients with tongue cancer based on a validated dataset comprising oral endoscopic images. We retrospectively constructed a dataset of 12,400 verified endoscopic images from five university hospitals in South Korea, collected between 2010 and 2020 with the participation of otolaryngologists. To calculate the probability of malignancy using various convolutional neural network (CNN) architectures, several deep learning models were developed. Of the 12,400 total images, 5576 images related to the tongue were extracted. The CNN models showed a mean area under the receiver operating characteristic curve (AUROC) of 0.845 and a mean area under the precision-recall curve (AUPRC) of 0.892. The results indicate that the best model was DenseNet169 (AUROC 0.895 and AUPRC 0.918). The deep learning model, general physicians, and oncology specialists had sensitivities of 81.1%, 77.3%, and 91.7%; specificities of 86.8%, 75.0%, and 90.9%; and accuracies of 84.7%, 75.9%, and 91.2%, respectively. Meanwhile, fair agreement between the oncologist and the developed model was shown for cancer diagnosis (kappa value = 0.685). The deep learning model developed based on the verified endoscopic image dataset showed acceptable performance in tongue cancer diagnosis.

Oncological Outcomes after Pulmonary Metastasectomy for Head and Neck Squamous-Cell Carcinoma and Adenoid Cystic Carcinoma.

INTRODUCTION: Pulmonary metastatic head and neck cancer has a poor prognosis. Pulmonary metastasectomy has been performed but only in carefully selected patients. The aim of this study was to examine the clinical characteristics and oncological follow-up of patients who underwent pulmonary metastasectomy. METHODS: Data of 54 patients with squamous-cell carcinoma (SCC) or adenoid cystic carcinoma (ACC) who underwent metastasectomy between 2003 and 2019 at two tertiary referral centers were retrospectively reviewed. RESULTS: The 3-year and 5-year disease-free survival rates after metastasectomy were 49.9% and 39.9% for SCC and 38.9% and 32.4% for ACC, respectively. Univariate analysis revealed that a disease-free interval (DFI) less than 14 months and R1 resection (hazard ratio [HR] [95% confidence interval]: 2.95 [0.77-5.62], 4.64 [0.99-21.65], respectively) were risk factors for recurrence in SCC and that a high T stage (HR: 5.24 [1.22-22.58]) was a risk factor in ACC. In SCC, a DFI less than 14 months and R1 resection (hazard ratio: 6.35 [1.36-29.54], 12.79 [1.53-106.95], respectively) were risk factors in a multivariate analysis. CONCLUSION: Pulmonary metastasectomy had a fair effect on head and neck SCC and ACC, and the prognosis was better in SCC patients with a DFI greater than 14 months.

Application of a strip design to monitor the viability of buried radial forearm free flap in East Asians: A case series study.

OBJECTIVES: The objectives of this study were to evaluate the reliability of a strip design as a monitoring flap in buried flap and to investigate whether strip design of radial forearm free flap (RFFF) could affect donor site morbidity in East Asian. METHODS: Patients with externalized flap in buried RFFF were consecutively included in this study. For cases with mucosal defect repair, a skin strip with a 1.5 cm width was proximally positioned to the primary flap along with the pedicle. Compared to a mucosal defect, a skin strip was distally positioned overlying the pedicle (near the wrist) when the flap was used for reinforcing the facial contour, reconstructing sacrificed facial nerve, or reanimating facial expression. The externalized flap formation was performed after completion of anastomoses of vessels. Monitoring results of flap failure using an externalized monitoring flap and additional morbidity of donor site were evaluated. RESULTS: Nine patients were included in this study. Although there were two cases of pharyngeal fistula due to mucosal necrosis of resection margin, transferred RFFF was viable in all cases. The externalized flap provided reliable monitoring for the buried RFFF without a case of necrosis even in two cases with a partial detachment of septocutaneous branches between the radial artery and the designed skin strip. There was no false - positive case. Therefore, the sensitivity and positive predictive value of the externalized monitoring flap were 100%. All defects of radial forearm caused by skin strip harvest were also primarily closed without an additional skin graft. CONCLUSION: A strip design for externalized monitoring flap in RFFF can facilitate an easier creation of externalized monitoring flap in cases with buried RFFF without additional morbidity at the donor site compared to a conventional techniques.

Feasibility and safety of neck level IB-sparing radiotherapy in nasopharyngeal cancer: a long-term single institution analysis.

PURPOSE: Nasopharyngeal cancer (NPC) has a higher prevalence of regional nodal metastasis than other head and neck cancers; however, level IB lymph node involvement is rare. We evaluated the safety and feasibility of level IB-sparing radiotherapy (RT) for NPC patients. MATERIALS AND METHODS: We retrospectively reviewed 236 patients with NPC who underwent definitive intensity-modulated RT with or without chemotherapy between 2004 and 2018. Of them, 212 received IB-sparing RT, and 24 received non-IB-sparing RT. We conducted a propensity score matching analysis to compare treatment outcomes according to IB-sparing status. In addition, dosimetric analysis of the salivary glands was performed to identify the relationship between xerostomia and the IB-sparing RT. RESULTS: The median follow-up duration was 78 months (range, 7 to 194 months). Local, regional, and distant recurrences were observed in 11.9%, 6.8%, and 16.1% of patients, respectively. Of the 16 patients with regional recurrence, 14 underwent IB-sparing RT. The most common site categorization of regional recurrence was level II (75%), followed by retropharyngeal lymph nodes (43.8%); however, there was no recurrence at level IB. In the matched cohorts, IB-sparing RT was not significantly related to treatment outcomes. However, IB-sparing RT patients received a significantly lower mean ipsilateral and contralateral submandibular glands doses (all, p < 0.001) and had a lower incidence of chronic xerostomia compared with non-IB-sparing RT patients (p = 0.006). CONCLUSION: Our results demonstrated that IB-sparing RT is sufficiently safe and feasible for treating NPC. To reduce the occurrence of xerostomia, IB-sparing RT should be considered without compromising target coverage.

Radiotherapy versus Surgery in Early-Stage HPV-Positive Oropharyngeal Cancer.

PURPOSE: This study aimed to compare the outcomes of primary radiotherapy (RT) versus surgery in early-stage human papilloma virus-positive oropharyngeal squamous cell carcinoma (hpv+OPC), and investigate the preoperative clinical factors that can predict the requirement for postoperative adjuvant treatment. MATERIALS AND METHODS: This multicenter study included 166 patients with American Joint Committee on Cancer 8th edition-Stages I-II hpv+OPC. Sixty (36.1%) and 106 (63.9%) patients underwent primary (concurrent chemo)radiotherapy [(CC)RT] and surgery, respectively. Seventy-eight patients (73.6%) in the surgery group received postoperative (CC)RT. RESULTS: With a median follow-up of 45.6 months for survivors, the 2-year overall survival (OS), progression-free survival (PFS), and locoregional control (LC) for RT/surgery were 97.8%/96.4%, 91.1%/92.0%, and 92.9%/93.3%, respectively. In multivariate analyses, patients with synchronous radiologic extranodal extension and conglomeration (ENEcong) of metastatic lymph nodes (LNs) showed significantly poorer OS (p=0.047), PFS (p=0.001), and LC (p=0.003). In patients undergoing primary surgery, two or more clinically positive LN metastases (odds ratio [OR], 5.15; p=0.004) and LN metastases with ENEcong (OR, 3.75; p=0.009) were predictors of postoperative chemoradiotherapy. No patient in the primary RT group demonstrated late severe toxicity whereas three (2.8%), one (0.9%), and one (0.9%) patient in the surgery group showed grade 3 dysphagia, grade 3 xerostomia, and fatal oral cavity bleeding. CONCLUSION: We found no differences in OS, PFS, and LC between upfront RT and surgery in stage I-II hpv+OPC which warrants comparison through a prospective trial in the treatment de-escalation era. However, most early-stage hpv+OPC patients undergoing surgery received adjuvant (CC)RT. Pretreatment LN findings were prognostic and predictive for adjuvant treatment.

Use of the comprehensive geriatric assessment for the prediction of postoperative complications in elderly patients with head and neck cancer.

BACKGROUND: To determine the efficacy of preoperative Comprehensive Geriatric Assessment (CGA) in predicting postoperative complications in elderly patients undergoing head and neck cancer surgery. METHODS: Medical records of patients aged ≥70 who underwent elective head and neck cancer surgery were reviewed. CGA scores were prospectively collected prior to surgery and analyzed to determine their association with postoperative complications. RESULTS: Of the 65 patients enrolled in this study, 34 (52.3%) with deficits in two or more preoperative CGA domains were categorized as "frail." Fourteen patients (21.5%) experienced postoperative complications. Age was not a risk factor for the complications (p = 0.504). The multivariate analysis indicated that major postoperative complications were significantly associated with frailty (odds ratio [OR] = 21.9, p = 0.039), operation time (OR = 39, p = 0.048), and estimated blood loss (OR = 19.8, p = 0.043). CONCLUSIONS: Frailty assessed by preoperative CGA, but not chronological age, was significantly associated with major postoperative complications in elderly patients undergoing head and neck cancer surgery.

Re-irradiation for recurrent or second primary head and neck cancer.

PURPOSE: To investigate the efficacy and safety of intensity-modulated radiotherapy (IMRT)-based re-irradiation (reRT) for recurrent or second primary head and neck cancer (HNC). MATERIALS AND METHODS: Patients who underwent IMRT-based reRT for recurrent or second primary HNC between 2007 and 2019 at two institutions were included. Medical records and dosimetric data were retrospectively reviewed. Overall survival (OS), progression-free survival (PFS), severe late toxicities, and clinicopathological prognostic factors were analyzed. RESULTS: A total of 42 patients were analyzed. With a median follow-up of 15.1 months (range, 3.7 to 85.8 months), the median OS was 28.9 months with a 2-year OS rate of 54.6%. The median PFS and 2-year PFS rates were 10.0 months and 30.9%, respectively. Multivariate analysis showed that good performance (Eastern Cooperative Oncology Group [ECOG] 0 or 1), a longer time interval (≥24 months) between radiotherapy courses, and higher reRT dose (>60 Gy) were significantly favorable factors for OS (all p < 0.05). Higher reRT dose and salvage surgery were significantly associated with improved PFS (all p < 0.05). Regarding the Multi-Institution Reirradiation (MIRI) Collaborative RPA classification, the 2-year OS rates of each class were 87.5% in class I, 51.8% in class II, and 0% in class III (p = 0.008). Grade ≥3 late toxicity was reported in 10 (23.8%) patients. There was no significant factor associated with increased late toxicities. CONCLUSION: IMRT-based reRT should be considered as a treatment option for patients with recurrent or second primary HNC. Further trials are needed to establish a subset of patients who may benefit from reRT without severe late toxicity.

Role of concurrent chemoradiation on locally advanced unresectable adenoid cystic carcinoma.

BACKGROUND/AIMS: Adenoid cystic carcinoma (ACC) is a rare salivary gland tumor characterized by indolence, with a high rate of local recurrence and distant metastasis. This study aimed to investigate the effect of concurrent chemoradiation (CCRT) on locally advanced unresectable ACC. METHODS: We retrospectively analyzed clinical data from 10 patients with pathologically confirmed ACC of the head and neck who received CCRT with cisplatin in Seoul National University Hospital between 2013 and 2018. RESULTS: Ten patients with unresectable disease at the time of diagnosis or with positive margins after surgical resection received CCRT with weekly cisplatin. Eight patients (80%) achieved complete remission, of which three later developed distant metastases without local relapse; one patient developed distant metastasis and local relapse. Two patient achieved partial remission without progression. Patients experienced several toxicities, including dry mouth, radiation dermatitis, nausea, and salivary gland inflammation of mostly grade 1 to 2. Only one patient showed grade 3 oral mucositis. Median relapse-free survival was 34.5 months (95% confidence interval, 22.8 months to not reached). CONCLUSION: CCRT with cisplatin is effective for local control of ACC with manageable toxicity and may be an effective treatment option for locally advanced unresectable ACC.

Usage and Diagnostic Yield of Fine-Needle Aspiration Cytology and Core Needle Biopsy in Thyroid Nodules: A Systematic Review and Meta-Analysis of Literature Published by Korean Authors.

OBJECTIVES: The usefulness of core needle biopsy (CNB) for the diagnosis of thyroid nodules remains controversial, and preferences vary across hospitals. The purpose of this study was to assess the actual use of CNB in Korea and to analyze the advantages and disadvantages of CNB through a systematic review and meta-analysis of papers published by Korean authors. METHODS: A meta-analysis of full-text publications published in English presenting data from Korea retrieved from the Embase literature database was performed. RESULTS: CNB led to a significantly lower proportion of non-diagnostic results than fine-needle aspiration (FNA). However, the frequency of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) did not decrease as a result of performing CNB in nodules with initial AUS/FLUS results while it increased in consecutive cases. A subcategory analysis of AUS/FLUS showed that the increased frequency of AUS/FLUS findings on CNB was due to more frequent diagnoses of architectural atypia and follicular neoplasm, which resulted in a higher frequency of inconclusive findings in consecutive cases compared to FNA. Hospitals favoring CNB had a higher proportion of AUS/FLUS diagnoses. Although the complication rate did not differ significantly between CNB and FNA, serious complications of CNB did occur. CONCLUSION: A reduced frequency of non-diagnostic results may be a definite advantage of CNB over FNA. However, the increased frequency of diagnoses of architectural atypia and follicular neoplasm should be considered when selecting CNB as a diagnostic tool.

Oncological outcomes of preoperatively unexpected malignant tumors of the parotid gland.

PURPOSE: Unexpected parotid cancers are often encountered due to inaccuracies in the preoperative evaluation. This study aimed to examine the clinical characteristics and oncological outcomes of these cancers and to propose the appropriate management strategy. METHODS: This is a multicenter case series study in which a total of 302 patients were diagnosed postoperatively with parotid cancers between 2003 and 2017. Of these, 85 cases without evidence of malignancy prior to surgery but identified as malignant on postoperative pathology were included. RESULTS: Of 85 patients, 76 and 9 underwent superficial and total parotidectomy, respectively. A positive resection margin was present in 24.7% of the cases. Postoperative radiotherapy was administered to 43.6% of patients; 4.2% had a local recurrence, and no patients died of the disease. The 5-year overall and relapse-free survival rates were 100.0% and 95.2%, respectively. Patients who underwent piecemeal resection had significantly poorer oncologic outcomes. Age, sex, histologic grade, T stage, extracapsular extension, resection margin status, and postoperative radiotherapy did not affect recurrence and survival. CONCLUSION: Preoperatively unexpected parotid cancers had excellent local control and overall survival despite positive or close resection margin, with or without postoperative radiotherapy. Therefore, patients with unexpected parotid malignancies may benefit from less aggressive postoperative management option.

Survival Benefits From Surgery for Stage IVa Head and Neck Squamous Cell Carcinoma: A Multi-institutional Analysis of 1,033 Cases.

OBJECTIVES: Head and neck squamous cell carcinomas (HNSCs) are frequently diagnosed at the locoregional advanced stage (stage IVa), but controversy remains regarding whether stage IVa HSNCs should be treated with upfront surgery or definitive chemoradiation therapy (CRT). The purpose of this study was to compare overall survival (OS) and disease-free survival (DFS) in patients with stage IVa HNSC treated primarily by surgery with curative intent with/without (neo)adjuvant treatment (surgery group) versus those treated primarily with CRT (CRT group). METHODS: We reviewed data of 1,033 patients with stage IVa HNSC treated with curative intent at 17 cancer centers between 2010 and 2016. RESULTS: Among 1,033 patients, 765 (74.1%) received upfront surgery and 268 (25.9%) received CRT. The 5-year OS and DFS rates were 64.4% and 62.0% in the surgery group and 49.5% and 45.4% in the CRT group, respectively. In multivariate analyses, OS and DFS were better in the surgery group than in the CRT group (odds ratio [OR] for death, 0.762; 95% confidence interval [CI], 0.592-0.981; OR for recurrence, 0.628; 95% CI, 0.492-0.802). In subgroup analyses, the OS and DFS of patients with oropharyngeal cancer were better in the surgery group (OR for death, 0.548; 95% CI, 0.341-0.879; OR for recurrence, 0.598; 95% CI, 0.377-0.948). In the surgery group, patients with laryngeal cancer showed better OS (OR for death, 0.432; 95% CI, 0.211-0.882), while those with hypopharyngeal cancer DFS was improved (OR for recurrence, 0.506; 95% CI, 0.328-0.780). CONCLUSION: A survival benefit from surgery may be achieved even in patients with stage IVa HNSC, particularly those with oropharyngeal and laryngeal cancer. Surgery led to a reduction in the recurrence rate in patients with hypopharyngeal cancer.

Estrogen receptor α as a predictive biomarker for survival in human papillomavirus-positive oropharyngeal squamous cell carcinoma.

BACKGROUND: Although oropharyngeal squamous cell carcinoma (OPSCC) with human papillomavirus (HPV) infection has a good prognosis, the accurate prediction of survival and risk of treatment failure is essential to design deintensification regimens. Here, we investigated estrogen receptor α (ERα) as a prognostic biomarker with therapeutic implications in OPSCC alongside factors associated with HPV infection. METHODS: We performed immunohistochemistry for ERα and p53 using formalin-fixed, paraffin-embedded tissues and assessed the HPV status using p16 immunohistochemistry and HPV DNA testing in 113 consecutive patients with OPSCC treated with surgical resection or radiotherapy/chemoradiotherapy. RESULTS: ERα expression and p53 alteration was observed in 35.4% and 21.2% OPSCCs; 45.6% and 1.3% p16+/HPV+ OPSCCs; and 11.5% and 76.9% p16- OPSCCs, respectively. These data suggest that OPSCC pathogenesis varies with HPV status. Furthermore, ERα expression was associated with improved overall survival (OS) in both HPV+ (p16+/HPV+ OPSCC) and p16+ (p16+ OPSCC irrespective of HPV status) models (p = 0.005 and p = 0.006, respectively) and with improved OS adjusted for stage (p = 0.037, hazard ratio: 0.109, 95% confidence interval 0.013-0.871) in the p16+ model. CONCLUSIONS: ERα is a potential predictive biomarker for improved survival in both HPV+ and p16+ OPSCC models.

The Effect of Prophylactic Central Neck Dissection During Hemithyroidectomy on Locoregional Recurrence in Patients With Papillary Thyroid Carcinoma: A Meta-Analysis.

OBJECTIVES: Hemithyroidectomy is commonly performed in patients with low- to intermediate-risk papillary thyroid carcinoma. The purpose of this meta-analysis was to evaluate the effect of prophylactic central neck dissection on locoregional recurrence in patients undergoing hemithyroidectomy. METHODS: A meta-analysis was performed of full-text publications published in English retrieved from the Embase database. RESULTS: The rate of regional recurrence in the central compartment after hemithyroidectomy, with or without prophylactic central neck dissection, was 0.17% and 1.78%, respectively. This difference was statistically significant. Recurrence in the lateral compartment or contralateral thyroid was not affected by prophylactic central neck dissection; the overall rate of recurrence was 1.3% and 5.4%, respectively. CONCLUSION: Prophylactic central neck dissection significantly reduced the risk of recurrence in the central compartment in patients undergoing hemithyroidectomy.

Adjuvant Postoperative CD40 Agonist and PD-1 Antagonist Combination Therapy in Syngeneic Tongue Cancer Mouse Model.

BACKGROUND/AIM: Using a syngeneic tongue cancer mouse model, the effect of CD40 agonist and PD-1 antagonist combination therapy for local recurrence after surgery was evaluated in a partially depleted CD4 model. MATERIALS AND METHODS: C3H/HeN mice were injected with 0.05 mg of the anti-mouse CD4 clone GK1.5, causing partial depletion of CD4 cells. Tongue cancer was induced by injecting the squamous cell carcinoma (SCC) VII cell line, the tumor was resected by partial glossectomy, and CD40 agonist and/or PD-1 antagonist therapy was administered postoperatively. RESULTS: Partial depletion of CD4 cells resulted in faster growth of a recurring tumor in the tongue, faster loss of body weight, and decreased number of CD8a-positive cells in the tumor. Postoperative adjuvant therapy with a combination of CD40 agonist and PD-1 antagonist resulted in a significant increase in survival compared to the CD40 agonist single treatment. CONCLUSION: CD40 agonist and PD-1 antagonist combination therapy could be an effective postoperative adjuvant treatment, especially in cases with decreased CD4 T cell activity.