Impact of dysplasia at resection margin on oncologic outcome after curative resection of oral tongue squamous cell carcinoma: significance of high-grade dysplastic resection margin.

BACKGROUND: This study aimed to compare the oncologic outcomes among negative, close, positive, and dysplasia resection margins (RMs) with oral tongue squamous cell carcinoma (OSCC) and to investigate the impact of dysplastic RMs. METHODS: The 565 patients were retrospectively analyzed and divided into four groups according to RM. Dysplasia was classified into mild, moderate, and severe subgroups. RESULTS: RMs consisted of negative (62.1%), close (27.1%), positive (2.1%), and dysplastic (8.7%). In multivariate analysis, advanced T/N stages and positive RM were significant risk factors for overall survival, while dysplasia at the RM was not a significant risk factor for locoregional recurrence or overall survival. In subgroup analysis of patients with dysplastic margin, RM with severe dysplasia showed higher recurrence than mild and moderate dysplasia. CONCLUSIONS: Dysplastic RM was not a risk factor for recurrence and survival. Severe dysplasia RM should be carefully observed due to higher recurrence compared to other dysplasia RMs.

Surgeon Volume and Long-Term Oncologic Outcomes in Patients with Medullary Thyroid Carcinoma.

BACKGROUND: Surgery is the most important curative treatment for medullary thyroid carcinoma (MTC). The relationship between surgeon volume (the number of surgeries performed) and short-term surgical outcomes, such as increased postoperative complication or costs, is well established. This study evaluated whether surgeon volume influenced long-term oncologic outcomes. METHODS: We retrospectively reviewed 246 patients diagnosed with MTC after initial thyroid surgery from 1995 to 2019. After exclusion, 194 patients were eligible for inclusion in the study. Surgeons were categorized as low/intermediate volume (fewer than 100 operations per year) or high volume (at least 100 operations per year). RESULTS: Of the 194 included patients, 60 (30.9%) developed disease recurrence, and 9 (4.6%) died of MTC during the median follow-up of 92.5 months. Having a low/intermediate-volume surgeon was associated with high disease recurrence (log-rank test, p < 0.001). After adjustment for age, sex, tumor type (sporadic versus hereditary), primary tumor size, presence of central lymph node metastasis (LNM), presence of lateral LNM, extrathyroidal extension, and positive resection margin, surgeon volume was a significant factor for disease recurrence (hazard ratio 2.28, p = 0.004); however, cancer-specific survival was not affected by surgeon volume (hazard ratio 4.16, p = 0.115). CONCLUSIONS: Surgeon volume is associated with long-term oncologic outcome. MTC patients will be able to make the best decisions for their treatment based on the results of this study.

Clinical outcomes of bulky parotid gland cancers: need for self-examination and screening program for early diagnosis of parotid tumors.

BACKGROUND: Early detection and diagnosis of parotid gland cancer (PGC) are essential to improve clinical outcomes, because Tumor-Node-Metastasis stage at diagnosis is a very strong indicator of prognosis in PGC. Nevertheless, some patients still present with large parotid mass, maybe due to the unawareness or ignorance of their disease. In this study, we aimed to present the clinical outcomes of bulky PGC (defined by a 4 cm cutoff point for T3-4 versus T1-2 tumors), to emphasize the necessity of a self-examination tool for parotid gland tumor. METHODS: We retrospectively reviewed 60 consecutive cases with bulky (equal to and greater than 4 cm in the longest diameter, determined radiologically) malignant tumors arising from the parotid gland from 1995 to 2016. The clinical and pathological factors were analyzed to identify risk factors for poor outcomes using Cox proportional hazard models. In addition, we designed a self-examination tool for parotid gland tumors, similar to breast self-examination for breast cancer detection. RESULTS: Patients with bulky parotid cancer showed 48.9% 5-year and 24.5% 10-year overall survival rates and a 47.9% risk of high-grade malignancy. The common pathological diagnoses were carcinoma ex pleomorphic adenoma (18.3%), adenocarcinoma (16.7%), mucoepidermoid carcinoma (16.7%), salivary duct carcinoma (16.7%), and adenoid cystic carcinoma (11.7%). Survival analyses revealed that tumor size (hazard ratio, HR = 1.262 upon increase of 1 cm, 95% confidence interval, 95%CI 1.059-1.502), lymph node metastasis (HR = 2.999, 95%CI 1.048-8.583), and high tumor grade (HR = 4.148, 95%CI 1.215-14.154) were independent prognostic factors in multivariable analysis. Functional preservation of the facial nerve was possible only in less than half of patients. CONCLUSION: In bulky PGC, lymph node metastasis at diagnosis and high tumor grade indicated poor survival outcomes, and functional outcomes of the facial nerve were suboptimal. Thus, a public effort seems to be necessary to decrease these patients with bulky PGC, and to increase patients' self-awareness of their disease. As a way of early detection, we proposed a parotid self-examination tool to detect parotid gland tumors at an early stage, which is similar to breast self-examination.

Randomized trial of prophylactic ipsilateral central lymph node dissection in patients with clinically node negative papillary thyroid microcarcinoma.

PURPOSE: This study aimed to evaluate the role of prophylactic ipsilateral central neck dissection (pCND) in patients with clinically node-negative (cN0) papillary thyroid microcarcinoma (PTMC). METHODS: In this randomized control trial, a total of 164 consecutive patients were enrolled. By double-blinded randomization protocol, patients were allocated into hemithyroidectomy with pCND (n = 82) or without pCND (n = 82). With intention-to-treat analysis, post-surgical pathological and clinical course, surgery-related complications, causes and clinical course of protocol-violated cases and 5-year recurrence-free survival were compared. RESULTS: Operation time, hospital stay, and post-surgical complication were not significantly different between the two groups. In the pCND (+) group, occult lymph node metastasis rate was 50.0%, and lymph node ratio (metastatic/harvested lymph nodes) was 45.2%. Ten patients in the pCND (+) group had converted to undergo onsite or staged completion total thyroidectomy due to the presence of metastatic central lymph nodes and/or positive resection margin. Until last follow-up (mean 73.4 months), one regional recurrence developed in the pCND (-) group, and three regional recurrences occurred in the pCND (+) group. Five-year recurrence-free survival was similar between the two groups. CONCLUSION: Although ipsilateral pCND could clear occult lymph node metastasis in the central compartment, it failed to provide any oncological benefit for cN0 PTMC patients.

The effect of 2D and 3D cell cultures on treatment response, EMT profile and stem cell features in head and neck cancer.

BACKGROUND: Head and Neck Squamous Cell Carcinoma (HNSCC) tumors are often resistant to therapies. Therefore searching for predictive markers and new targets for treatment in clinically relevant in vitro tumor models is essential. Five HNSCC-derived cell lines were used to assess the effect of 3D culturing compared to 2D monolayers in terms of cell proliferation, response to anti-cancer therapy as well as expression of EMT and CSC genes. METHODS: The viability and proliferation capacity of HNSCC cells as well as induction of apoptosis in tumor spheroids cells after treatment was assessed by MTT assay, crystal violet- and TUNEL assay respectively. Expression of EMT and CSC markers was analyzed on mRNA (RT-qPCR) and protein (Western blot) level. RESULTS: We showed that HNSCC cells from different tumors formed spheroids that differed in size and density in regard to EMT-associated protein expression and culturing time. In all spheroids, an up regulation of CDH1, NANOG and SOX2 was observed in comparison to 2D but changes in the expression of EGFR and EMT markers varied among the cell lines. Moreover, most HNSCC cells grown in 3D showed decreased sensitivity to cisplatin and cetuximab (anti-EGFR) treatment. CONCLUSIONS: Taken together, our study points at notable differences between these two cellular systems in terms of EMT-associated gene expression profile and drug response. As the 3D cell cultures imitate the in vivo behaviour of neoplastic cells within the tumor, our study suggest that 3D culture model is superior to 2D monolayers in the search for new therapeutic targets.

Comparison of prognostic implications between the 7th and 8th edition of AJCC TNM staging system for head and neck soft-tissue sarcoma in adult patients.

PURPOSE: This study aimed to investigate the prognostic factors for head and neck soft-tissue sarcoma (HNSTS) in adults, with the comparisons between the 7th and 8th edition of AJCC TNM staging system. METHODS: From a cancer registry of a single, tertiary referral medical center, the medical records of 67 patients treated from February 2005 to December 2017 were reviewed. RESULTS: T1b stage by AJCC 7th edition showed most diverse stage migration by AJCC 8th edition, and T1a or T2b stage by 7th edition remained in T1-3 or T3-4 by 8th edition. T2 stage by 7th edition showed a significantly higher death rate than the T1 stage, with fair discrimination in overall survival. Higher histologic grade and angiosarcoma were significant prognostic factors for recurrence as well as overall survival. Also, nodal and distant metastasis worsen overall survival. CONCLUSIONS: In our series of patients with HNSTS, higher histologic grade, angiosarcoma, N1, and M1 stage significantly increased the risk of recurrence and worse overall survival, which was not evident in revised T stage by AJCC 8th edition.

Incidence of postoperative facial weakness in parotid tumor surgery: a tumor subsite analysis of 794 parotidectomies.

BACKGROUND: The reported incidence of facial weakness immediately after parotid tumor surgery ranges from 14 to 65%. The purpose of this study was to evaluate the incidence of postoperative facial weakness related to parotidectomy with use of preoperative computed tomography (CT), intraoperative facial nerve monitoring, and surgical magnification. Also, we sought to elucidate additional information about risk factors for postoperative facial weakness in parotid tumor surgery, particularly focusing on the tumor subsites. METHODS: We retrospectively reviewed 794 cases with parotidectomy for benign and malignant tumors arising from the parotid gland (2009-2016). Patients with pretreatment facial palsy were excluded from the analyses. Tumor subsites were stratified based on their anatomical relations to the facial nerve as superficial, deep, or both. Multivariable logistic regression analyses were conducted to identify risk factors for postoperative facial weakness. RESULTS: The overall incidences of temporary and permanent (more than 6 months) facial weakness were 9.2 and 5.2% in our series utilizing preoperative CT, intraoperative facial nerve monitoring, and surgical magnification. Multivariable analysis revealed that old age, malignancy, and recurrent tumors (revision surgery) were common independent risk factors for both temporary and permanent postoperative facial weakness. In addition, tumor subsite (tumors involving superficial and deep lobe) was associated with postoperative facial weakness, but not tumor size. Extent of surgery was strongly correlated with tumor pathology (malignant tumors) and tumor subsite (tumors involving deep lobe). CONCLUSION: Aside from risk factors for facial weakness in parotid tumor surgery such as old age, malignant, or recurrent tumors, the location of tumors was found to be related to postoperative facial weakness. This study result may provide background data in a future prospective study and up-to-date information for patient counseling.

Molecular genotyping of the non-invasive encapsulated follicular variant of papillary thyroid carcinoma.

AIMS: The non-invasive encapsulated follicular variant of papillary thyroid carcinoma (FVPTC) has been managed as a low-risk malignancy. Recently, a proposal was made to reclassify this tumour type as a premalignant lesion and rename it non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This study aims to provide the first comprehensive study on molecular genotype-phenotype correlations of encapsulated FVPTC. METHODS AND RESULTS: This study was performed on 177 consecutive FVPTCs from January 2014 to April 2016. These were classified as non-invasive encapsulated FVPTC (n = 74) invasive encapsulated FVPTC (n = 51), and infiltrative FVPTC (n = 52), according to standard criteria, by two independent pathologists. Genetic alterations and other clinicopathological information were compared. BRAFV600E was found in 12.2% (non-invasive) and 11.8% (invasive) of encapsulated FVPTCs, and in 34.6% of infiltrative FVPTCs (P = 0.001). Mutation in encapsulated FVPTCs was limited to cases with rare or abortive papillae. RET-PTC1 and RET-PTC3 rearrangements were present (11.5%) only in infiltrative FVPTCs. In contrast, NRAS, HRAS and KRAS mutations were observed more often in encapsulated FVPTCs (48.6% in non-invasive and 66.7% in invasive) than in infiltrative FVPTCs (15.4%) (P < 0.001). Preoperative cytological examination did not distinguish between non-invasive and invasive encapsulated FVPTCs, whereas infiltrative FVPTC was more likely to be Bethesda class V/VI than the encapsulated type (60.4% versus 38.1%; P = 0.01). CONCLUSIONS: There were no differences in clinicopathological or molecular profiles between non-invasive and invasive encapsulated FVPTCs, except in vascular and capsular invasion. Therefore, the diagnosis of NIFTP, like that of follicular adenoma, may require surgical resection and exclusion of those tumours with any papillae.

Treatment outcomes in metastatic and localized high-grade salivary gland cancer: high chance of cure with surgery and post-operative radiation in T1-2 N0 high-grade salivary gland cancer.

BACKGROUND: High-grade salivary gland cancer is a distinct clinical entity that has aggressive disease progression and early systemic spread. However, because of the rarity of the disease, the clinical outcomes, prognostic factors and clinical decision on the optimal treatments have not been fully understood. METHODS: In this study, we retrospectively analyzed the clinical data of 124 patients with high-grade salivary gland cancers and performed multivariate survival analyses to evaluate the clinico-pathological factors affecting the treatment outcomes. RESULTS: The 5-year disease-specific survival was 63.4% in patients with high-grade salivary gland cancers. Among the clinico-pathological factors, presence of lymph node metastasis (hazard ratio 5.63, 95% confidence interval 2.64-12.03, P < 0.001) and distant metastasis (hazard ratio 4.59, 95% confidence interval 2.10-10.04, P < 0.001) at diagnosis were the most potent unfavorable prognostic factors. Importantly, patients with early-stage disease (T1-2N0M0) showed apparently a relatively excellent prognosis (93.2% 5-year disease-specific survival); meanwhile N (+) and M1 status at diagnosis resulted in dismal outcomes (44.6 and 21.1% 5-year disease-specific survival, respectively). On comparing surgery alone as a treatment modality, surgery plus postoperative radiation significantly benefited the patients, but the difference between adjuvant radiation and chemoradiation was not found to be significant. Pathological subtypes of high-grade salivary gland cancers were not significantly associated with prognosis. CONCLUSIONS: Despite of an overall unfavorable prognosis in high-grade salivary gland cancer, patients with early-stage disease are expected to have excellent prognosis (over 90% survival rates) with surgery plus adjuvant radiation, which may implicate the patients' consultation, therapeutic decision making, and the need for early detection of the disease.

Differential Impact of Close Surgical Margin on Local Recurrence According to Primary Tumor Size in Oral Squamous Cell Carcinoma.

BACKGROUND: The extent of surgical safety margin (gross tumor border to resection margin) in oral cancer surgery remains unclear, and no study has determined the differential impact of close surgical margin and microscopic extension according to primary tumor size in oral cancers. METHODS: We retrospectively analyzed the clinical data of 325 patients with surgically treated oral cavity squamous cell carcinomas to determine the effect of a close surgical margin (<5 mm) (cSM5) on local recurrence. In addition, the depth of microscopic tumor infiltration was determined in 90 available surgical specimens. RESULTS: The cSM5 was not related to the risk of local tumor recurrence in early-stage oral cancer, while it significantly increased the rate of local tumor recurrence in resectable advanced-stage oral cancers (hazard ratio 3.157, 95 % confidence interval 1.050-9.407, p = 0.041). Addition of postoperative adjuvant radiation to early-stage tumors with cSM5 did not further reduce the local recurrence rate compared to surgery alone. The depth of microscopic tumor extension from the gross tumor border was significantly associated with primary tumor thickness (ρ = 0.390, p < 0.001) and tumor sizes (ρ = 0.308, p = 0.003), which was a median (range) of 0.84 (0.14-2.32) mm in T1, 1.06 (0.20-4.34) mm in T2, and 1.77 (0.13-4.70) mm in T3-4. CONCLUSIONS: The cSM5 was a significant risk factor for local recurrence only in advanced oral cancers, but not in early-stage tumors, where microscopic tumor extension was not beyond 3 mm in T1 tumors. Thus, the extent of surgical safety margin can be redefined according to the primary tumor size.

Prognostic factors for recurrence of locally advanced differentiated thyroid cancer.

Background and Objectives To present treatment outcomes and prognostic factors for surgical management of locally advanced differentiated thyroid cancer (DTC). METHODS: Retrospective review of 70 patients in a single, tertiary referral institution was done. Clinical pathology characteristics were analyzed to investigate prognosticators, based on primary endpoints; locoregional recurrence alone (LRR), total recurrence (LRR or distant metastasis (DM)), and recurrence-free survival. RESULTS: Recurrent laryngeal nerve (n = 31) and trachea (n = 30) were most commonly invaded organs by tumor. At the mean follow-up of 81.7 months, LRR occurred in 15 patients and/or DM was detected in 15 patients (10 developed LRR and DM). By multivariate analysis, R1 resection (positive margin) and pN1b stage increased risk of LRR with a fold of 3.16 [95%CI 1.08-9.24, P = 0.03] and 5.92 [1.61-21.7, P = 0.007], respectively. Also, they increased risk of total recurrence with a fold of 3.04 [95%CI 1.26-7.31, P = 0.01] and 3.42 [95%CI 1.16-10.0, P = 0.02], respectively. Patients with pN1b stage showed better LRR-free survival than pN0/N1a stage (P = 0.03). Conclusions Along with careful preoperative evaluation of the extent of primary and neck disease, obtaining negative resection margin and aggressive neck management is critical to improve oncologic outcomes of locally advanced DTC.

Impact of Dietary Intake and Habits on Subjective Voice and Laryngeal Mucosal Diseases: Analysis From Korean National Health and Nutritional Examination Survey Between 2008 and 2021.

OBJECTIVES: Dysphonia negatively affects social communication, leading to reduced quality of life. Comprehensive research on dysphonia and laryngeal mucosal diseases using large-scale epidemiological data is lacking. Therefore, we investigated how dietary and habitual factors influence dysphonia and laryngeal mucosal diseases using data from the Korean National Health and Nutritional Examination Survey. STUDY DESIGN: A population-based cross-sectional study. METHODS: The study included individuals aged 19 years and older who both underwent laryngoscopic examinations and completed a dysphonia survey. Dietary and habitual factors and results of the laryngoscopic examinations were collected. Risk factors for dysphonia and laryngeal mucosal diseases were identified. RESULTS: The weighted frequency of dysphonia and laryngeal mucosal diseases was 6.4% and 6.0%, respectively. In univariable analyses for dysphonia, sex, body weight change, alcohol ingestion, and various minerals and vitamins showed statistically significant associations. However, in the multivariable analysis, only age, body weight, female sex, and vitamin A intake were significantly associated with dysphonia. Age, body weight, body mass index, sex, smoking, amount of sodium intake, and alcohol intake were associated with laryngeal mucosal diseases in the univariable analyses, but in the multivariable analysis, only age, smoking, and amount of niacin intake were significant factors. CONCLUSIONS: In this large-scale epidemiological analysis, subjective dysphonia and laryngeal mucosal diseases had different frequencies and risk factors. Age was a risk factor for both dysphonia and mucosal diseases, but smoking was only a risk factor for laryngeal mucosal diseases. Diet types, calories, and water and alcohol intake were not significant risk factors for either laryngeal mucosal diseases or dysphonia.

Clinical Outcomes in Adenoid Cystic Carcinoma of the Nasal Cavity and Paranasal Sinus: A Comparative Analysis of Treatment Modalities.

This study aimed to present the treatment patterns and outcomes for adenoid cystic carcinoma (ACC) arising in the nasal cavity and paranasal sinus. Sixty-one sinonasal ACC patients were retrospectively reviewed: 31 (50.8%) underwent surgery followed by postoperative radiation therapy (S+PORT), and 30 (49.2%) received definitive radiation therapy (D(C)RT). T4 disease was significantly more frequent in the D(C)RT group (25.8% vs. 80.0%, p < 0.001), where all T4b disease patients underwent D(C)RT. The 5-year local failure-free survival (LFFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival were 61.8% versus 37.8% (p = 0.003), 64.8% versus 38.1% (p = 0.036), 52.6% versus 19.3% (p = 0.010), and 93.2% versus 73.4% (p = 0.001) in the S+PORT and D(C)RT groups, respectively. The absolute differences in 5-year rates of LFFS, DMFS, and PFS between the two groups were smaller in the T3-4 subgroup. The univariate analysis showed that T4b disease, neurologic symptoms, longest diameter of tumor, radiological evidence of nerve involvement, and undergoing D(C)RT were associated with worse clinical outcomes, but the significance disappeared in the multivariate analysis, except for in the case of radiological evidence of nerve involvement. In conclusion, most patients with extensive disease underwent upfront D(C)RT and generally exhibited inferior clinical outcomes when compared to those with less extensive disease and who underwent S+PORT.

Extent of local invasion and safe resection in cT1-2 tonsil cancer.

BACKGROUND: Although intraoral resection of small-sized tonsil cancer achieves excellent tumor control, the extent of local invasion and adequate safety margin in resection have not been studied. Thus, we aim to determine the extent of local invasion in terms of mucosal spread and deep infiltration in stage T1-2 tonsil cancer. METHODS: We re-analyzed the surgical specimens from 49 cT1-2 tonsil cancers. Microscopic tumor cell extension from the tumor gross boundary of specimens was assessed in representative sections of each tumor. We also tested whether local extension correlates with human papilloma virus (HPV) status of tumors. RESULTS: The extent of microscopic deep invasion from the gross tumor border was 0.52 ± 0.41 mm, which was significantly less than that of mucosal spread (0.83 ± 0.61 mm, P = 0.01) in cT1-2 tonsil cancer. The microscopic deep invasion correlated with tumor size (rho = 0.703, P < 0.001). We found tumor invasion into superior constrictor muscles in 58.1%, no cases of tumor invasion into the deep fascia. In terms of HPV status (genotyping plus p16 staining), there were no differences in microscopic tumor extension. CONCLUSION: Our detailed pathologic analyses confirm that an oropharyngectomy including the superior constrictor muscle is an oncologically safe procedure for stage T1-2 tonsil cancer.

Prognostic Significance of the Post-Treatment Neutrophil-to-Lymphocyte Ratio in Pharyngeal Cancers Treated with Concurrent Chemoradiotherapy.

BACKGROUND: Even though the pre-treatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are well-established prognosticators in various cancers including head and neck cancers, there have been relatively few studies on the clinical significance of the post-treatment values. This study aimed to investigate the changes in NLR and PLR after concurrent chemoradiotherapy (CCRT) and to evaluate their prognostic significance in pharyngeal cancers. METHODS: This study was retrospectively conducted on 461 consecutive patients with primary pharyngeal cancer who had received definitive CCRT. Blood test results before and after CCRT were obtained, and the pre- and post-treatment NLR and PLR were calculated. Patient prognosis was evaluated based on overall survival (OS) and relapse-free survival (RFS). RESULTS: After CCRT, the NLR increased from 2.01 (interquartile range (IQR), 1.53-2.62) to 2.69 (IQR, 1.93-3.81), and the PLR increased from 118.84 (IQR, 92.61-151.63) to 193.19 (IQR, 146.28-262.46). Along with high pre-treatment NLR and high pre-treatment PLR, high post-treatment NLR was also significantly associated with worse OS and RFS (p = 0.013 and p = 0.026). In addition, patients with a high ΔNLR (i.e., the difference between pre- and post-treatment NLRs) had significantly worse OS and RFS (p = 0.013 and p = 0.026). However, only a high pre-treatment NLR (hazard ratio (HR), 2.19; 95% confidence interval (CI), 1.17-4.08; p = 0.014), age (HR, 2.16; 95% CI, 1.14-4.08; p = 0.018), and stage IV (HR, 2.11; 95% CI, 1.15-3.89; p = 0.017) were independent prognostic factors for OS in the multivariate analysis. CONCLUSIONS: In patients with pharyngeal cancers, following CCRT, the NLR and PLR increased significantly from pre-treatment values. Like the pre-treatment NLR and PLR, a high post-treatment NLR and a significant increase in NLR were also associated with poor prognosis. Further prospective studies are required to prove the independent significance of the post-treatment NLR and PLR.

Vascularized osseous flaps for head and neck reconstruction: Comparative analysis focused on complications and salvage options.

OBJECTIVES: This study aimed to compare the clinical outcomes of fibular (FFF group) and scapular (SFF group) osseous free flaps for reconstructing head and neck defects for primary surgery and salvage options. METHODS: We analyzed 156 cases of osseous free flaps in 138 patients from a retrospective review of a single institutional database between January 1996 and January 2020 (FFF, 114 cases in 99 patients; SFF, 42 cases in 39 patients). Clinical profiles such as age, sex, primary tumor site, and defect type were investigated in the two groups. In addition, the incidences and types of perioperative complications, flap compromise, and salvage management were compared between the two groups. RESULTS: FFF was used mostly for oromandibular defects, whereas SFF was preferred for maxillary defect reconstruction. The length of hospital stay was longer in the FFF group than in the SFF group. The flap compromise rate was not significantly different between the two groups; however, donor-site complications were not observed in the SFF group as compared to 7.9% in the FFF group. A regional or free (musculo) cutaneous flap was used as a salvage procedure in partial flap compromise. Contralateral SFF was available to replace a completely compromised SFF, whereas it was not feasible in a completely compromised FFF. Cox proportional hazards analysis showed no significant prognostic factors for flap-related complications. CONCLUSION: The two osseous free flaps showed differences in defect type, flap donor complications, and options for compromised flap salvage. These findings must be considered carefully in the preoperative planning stage to guarantee early recovery and timely administration of postoperative adjuvant treatment if necessary.

Can Definitive Radiation Therapy Substitute Surgical Resection in Locally Advanced T3 or T4 Sinonasal Squamous Cell Carcinoma?

PURPOSE: This study aimed to compare oncologic outcomes between definitive radiation therapy (RT) and upfront surgical resection in patients with sinonasal squamous cell carcinoma (SCC). METHODS AND MATERIALS: Between 2008 and 2021, 155 patients with T1-4b, N0-3 sinonasal SCC were analyzed. The 3-year overall survival (OS), local progression-free survival (LPFS), and overall progression-free survival (PFS) were evaluated using the Kaplan Meier method and compared using a log-rank test. A pattern of regional neck lymph node (LN) failure and treatment-related toxicity profiles were investigated. RESULTS: A total of 63 and 92 patients underwent upfront RT (RT group) and surgical resection (Surgery group), respectively. The RT group included significantly more patients with T3-4 disease than the Surgery group (90.5% vs 39.1%, P < .001). The rates of 3-year OS, LPFS, and PFS in the RT and Surgery groups were 68.6% versus 81.7% (P = .073), 62.3% versus 73.8% (P = .187), and 47.4% versus 66.1% (P = .005), respectively. However, the corresponding rates in patients with T3-4 disease were 65.1% versus 64.8% (P = .794), 57.4% versus 56.8% (P = .351), and 43.2% versus 46.5% (P = .638), respectively, demonstrating no statistically significant differences between the 2 treatment modalities. Among the 133 N0 patients, regional neck LN progression was observed in 17 patients, and the most common sites of regional neck LN failure were ipsilateral levels Ib (9 patients) and II (7 patients). The 3-year neck node recurrence-free rate in cT1-3N0 patients was 93.5%, while that in cT4N0 patients was 81.1% (P = .025). CONCLUSIONS: Upfront RT may be considered in selected patients with locally advanced sinonasal SCC, as we have demonstrated similar oncologic outcomes to those of surgery. Prophylactic neck treatment in T4 disease requires further investigation to evaluate its efficacy.

Clonal evolution of long-term expanding head and neck cancer organoid: Impact on treatment response for personalized therapeutic screening.

OBJECTIVES: In biobanking based on patient-derived organoids (PDO), the genetic stability of organoid lines is critical for the clinical relevance of PDO with parental tumors. However, data on mutational heterogeneity and clonal evolution of PDO and their effects on treatment response are insufficient. METHODS: To investigate whether head and neck cancer organoids (HNCOs) could maintain the genetic characteristics of their original tumors and elucidate the clonal evolution process during a long-term passage, we performed targeted sequencing, covering 377 cancer-related genes and adopted a sub-clonal fraction model. To explore therapeutic response variability between an early and late passage (>passage 6), we generated dose-response curves for drugs and radiation using two HNCO lines. RESULTS: Using 3D ex vivo organoid culture protocol, we successfully established 27 HNCOs from 39 patients with an overall success rate of 70% (27/39). Their mutational profiles were highly concordant, with three of the HNCOs analyzed showing greater than 70% concordance. Only one HNCO displayed less than 50% concordance. However, many of these organoid lines displayed clonal evolution during serial passaging, although major cancer driver genes and VAF distributions were shared between early and later passages. We also found that all late passages of HNCOs tended to be more sensitive to radiation than early passages, similar to drug response results. CONCLUSIONS: We report the establishment of HNCO lines derived from 27 patients and demonstrate their genetic concordance with corresponding parental tumors. Furthermore, we show serial changes in mutational profiles of HNCO along with long passage culture and the impact of these clonal evolutions on response to radiotherapy.

Imaging of Facial Nerve With 3D-DESS-WE-MRI Before Parotidectomy: Impact on Surgical Outcomes.

OBJECTIVE: The intra-parotid facial nerve (FN) can be visualized using three-dimensional double-echo steady-state water-excitation sequence magnetic resonance imaging (3D-DESS-WE-MRI). However, the clinical impact of FN imaging using 3D-DESS-WE-MRI before parotidectomy has not yet been explored. We compared the clinical outcomes of parotidectomy in patients with and without preoperative 3D-DESS-WE-MRI. MATERIALS AND METHODS: This prospective, non-randomized, single-institution study included 296 adult patients who underwent parotidectomy for parotid tumors, excluding superficial and mobile tumors. Preoperative evaluation with 3D-DESS-WE-MRI was performed in 122 patients, and not performed in 174 patients. FN visibility and tumor location relative to FN on 3D-DESS-WE-MRI were evaluated in 120 patients. Rates of FN palsy (FNP) and operation times were compared between patients with and without 3D-DESS-WE-MRI; propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to adjust for surgical and tumor factors. RESULTS: The main trunk, temporofacial branch, and cervicofacial branch of the intra-parotid FN were identified using 3D-DESS-WE-MRI in approximately 97.5% (117/120), 44.2% (53/120), and 25.0% (30/120) of cases, respectively. The tumor location relative to FN, as assessed on magnetic resonance imaging, concurred with surgical findings in 90.8% (109/120) of cases. Rates of temporary and permanent FNP did not vary between patients with and without 3D-DESS-WE-MRI according to PSM (odds ratio, 2.29 [95% confidence interval {CI} 0.64-8.25] and 2.02 [95% CI: 0.32-12.90], respectively) and IPTW (odds ratio, 1.76 [95% CI: 0.19-16.75] and 1.94 [95% CI: 0.20-18.49], respectively). Conversely, operation time for surgical identification of FN was significantly shorter with 3D-DESS-WE-MRI (median, 25 vs. 35 min for PSM and 25 vs. 30 min for IPTW, P < 0.001). CONCLUSION: Preoperative FN imaging with 3D-DESS-WE-MRI facilitated anatomical identification of FN and its relationship to the tumor during parotidectomy. This modality reduced operation time for FN identification, but did not significantly affect postoperative FNP rates.

Detection of Cancer Recurrence Using Systemic Inflammatory Markers and Machine Learning after Concurrent Chemoradiotherapy for Head and Neck Cancers.

Pretreatment values of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) are well-established prognosticators in various cancers, including head and neck cancers. However, there are no studies on whether temporal changes in the NLR and PLR values after treatment are related to the development of recurrence. Therefore, in this study, we aimed to develop a deep neural network (DNN) model to discern cancer recurrence from temporal NLR and PLR values during follow-up after concurrent chemoradiotherapy (CCRT) and to evaluate the model's performance compared with conventional machine learning (ML) models. Along with conventional ML models such as logistic regression (LR), random forest (RF), and gradient boosting (GB), the DNN model to discern recurrences was trained using a dataset of 778 consecutive patients with primary head and neck cancers who received CCRT. There were 16 input features used, including 12 laboratory values related to the NLR and the PLR. Along with the original training dataset (N = 778), data were augmented to split the training dataset (N = 900). The model performance was measured using ROC-AUC and PR-AUC values. External validation was performed using a dataset of 173 patients from an unrelated external institution. The ROC-AUC and PR-AUC values of the DNN model were 0.828 ± 0.032 and 0.663 ± 0.069, respectively, in the original training dataset, which were higher than the ROC-AUC and PR-AUC values of the LR, RF, and GB models in the original training dataset. With the recursive feature elimination (RFE) algorithm, five input features were selected. The ROC-AUC and PR-AUC values of the DNN-RFE model were higher than those of the original DNN model (0.883 ± 0.027 and 0.778 ± 0.042, respectively). The ROC-AUC and PR-AUC values of the DNN-RFE model trained with a split dataset were 0.889 ± 0.032 and 0.771 ± 0.044, respectively. In the external validation, the ROC-AUC values of the DNN-RFE model trained with the original dataset and the same model trained with the split dataset were 0.710 and 0.784, respectively. The DNN model with feature selection using the RFE algorithm showed the best performance among the ML models to discern a recurrence after CCRT in patients with head and neck cancers. Data augmentation by splitting training data was helpful for model performance. The performance of the DNN-RFE model was also validated with an external dataset.