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.

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.

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.

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.

Discrepancy between cTNM and pTNM staging of oral cavity cancers and its prognostic significance.

INTRODUCTION: Accurate tumor-node-metastasis(TNM) staging of oral cavity cancer(OCC) is very important in the management of this dismal disease. However, stage migration from cTNM to pTNM was found in a portion of OCC patients. The objective of this study was to determine the possible causes of discrepancy between cTNM and pTNM in OCC and the clinical impacts of stage migration. METHODS: Clinical and pathological data of 252 OCC patients were retrospectively reviewed and compared each other. Clinical staging was determined through the multidisciplinary evaluation of pre-treatment work-ups including PET/CT. In addition, we compared the up-staged cases with those in the no-change group with the same pTNM stages to identify the clinical impacts of such change. RESULTS: Clinical staging yielded overall 82.5% diagnostic accuracy in predicting pathological tumor status, and tumor extent was under-estimated in 9.5-13.5% of cases. The main causes of T up-staging were under-estimation of surface dimension (62.5%) and deep invasion to tongue extrinsic muscles (37.5%). N up-staging was due to occult single (57.6%) and multiple (42.4%) metastases. Surprisingly, TNM up-staging in our series did not have prognostic significance under the current management protocol. CONCLUSION: Clinical under-estimation of pathological tumor extent occurred in approximately 13% of OCC, without clinical impacts on prognosis.

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.

High-throughput profiling identifies clinically actionable mutations in salivary duct carcinoma.

BACKGROUND: Salivary duct carcinoma (SDC) is a highly aggressive subtype of salivary gland cancers and there is no established standard therapy for this disease. Thus, development of molecular markers for SDC will be important to guide the diagnosis and therapy of this aggressive tumor. METHODS: We performed next-generation sequencing using the Ion Torrent AmpliSeq cancer panel, which explores the mutational status of hotspot regions in 50 cancer-associated genes, and we analyzed copy number variations (CNVs) of 21 genes by NanoString nCounter for 37 patients with SDC. Fluorescent in situ hybridization was also conducted to confirm ERBB2 gene amplification. Clinical records and tumor histopathology of the patients were retrospectively reviewed. RESULTS: Genetic alterations were detected in 29 of 37 (78.3%) tumors, including mutations in PIK3CA (N = 9, 24.3%), ERBB2 (N = 4, 10.8%), and EGFR (N = 4, 10.8%). To our knowledge, this is the first time that ERBB2 mutations have been reported in this tumor type. Both PIK3CA and ERBB2 mutation status were associated with poor overall survival, but without statistical significance. ERBB2 amplification was strong and common in SDC and almost all cases also exhibited EGFR and ERBB3 amplifications. CONCLUSIONS: This study reports the largest and most comprehensive analysis of DNA aberrations in SDC. Our results show that PIK3CA and/or ERBB2 alterations in the development of SDC might be a useful diagnostic tool and could serve as a potential therapeutic target.

Diagnostic accuracy of fine needle aspiration cytology for high-grade salivary gland tumors.

BACKGROUND: Preoperative differentiation between high-grade malignancy and others (benign or low-grade tumors) is more important than differentiation between malignant and benign tumors for surgical planning, treatment outcome, and prognosis in salivary gland tumors. Fine needle aspiration cytology (FNAC) has a relatively low sensitivity for differentiating malignant from benign salivary tumors. However, the diagnostic performance of FNAC has not been studied in predicting high-grade salivary malignancy, which can significantly affect patient care. METHODS: Experienced cytopathologists reevaluated the adequate FNAC on 521 salivary gland tumors. The diagnostic performances of FNAC for total malignancy and high-grade malignancy were calculated, and the results were validated in independent 105 cases. In cases of high-grade cancer on FNAC, we recorded the additional diagnostic procedures and the change of surgical extent to decide how FNAC impacts clinical practice. RESULTS: The sensitivity, specificity, and diagnostic accuracy of FNAC in differentiating malignant from benign tumors were 64.2 % (95 % confidence interval 52.3-75.0), 98.4 % (96.5-99.3), and 92.1 % (89.1-94.6). Meanwhile, FNAC predicted high-grade malignancy accurately (94.6 % [80.0-99.5], 99.2 % [97.8-99.7], 98.9 % [97.3-99.6], respectively), a finding reproduced with similar results in the validation set. FNAC indicative of high-grade malignancy added additional imaging assessments in 94.9 %, frozen biopsy samples during surgery (tumor and lymph nodes) in 71.2 %, and changed the extent of surgery in 59.0 %. CONCLUSIONS: FNAC has an excellent diagnostic performance in discriminating high-grade salivary cancer, which guides clinical decision and surgical planning in salivary gland tumors.

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.

Comparison of 18F-fluorodeoxyglucose uptake with the expressions of glucose transporter type 1 and Na+/I- symporter in patients with untreated papillary thyroid carcinoma.

PURPOSE: Discrepancies between the uptakes of (18)F-fluorodeoxyglucose ((18)F-FDG) and (131)I in papillary thyroid carcinoma have been reported. We compared 18F-FDG uptake with the expressions of glucose transporter type 1 (GLUT1) and sodium-iodide symporter (NIS) in untreated papillary thyroid carcinoma. MATERIALS AND METHODS: A total of 33 consecutive patients (male:female = 12:21; mean age, 46.6 ± 13.0 years) with initially diagnosed papillary thyroid carcinoma were prospectively included in the study. All subjects underwent preoperative (18)F-FDG positron emission tomography/computerized tomography scans followed by surgery. The expressions of GLUT1 and NIS were evaluated in resected primary tumors and metastatic lymph nodes by immunohistochemical staining and were compared with the maximum standard uptake value of each lesion, respectively. RESULTS: None of the 40 primary tumors showed significant expressions of GLUT1. Significant expressions of NIS were found in 14 primary tumors (35.0%). Among 36 metastatic lymph nodes, only 1 showed GLUT1 expression. Significant expression of NIS was found in 13 (36.1%) metastatic nodes. The maximum standard uptake value of both primary tumors and metastatic nodes with negative expression of NIS was significantly higher than those with a positive expression of NIS (10.6 ± 10.8 vs. 4.9 ± 5.2, p = 0.011). CONCLUSIONS: The 18F-FDG uptake of untreated papillary thyroid carcinoma has an inverse correlation with NIS expression. However, GLUT1 expression does not appear to be associated with 18F-FDG uptake in untreated papillary thyroid carcinoma.

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.

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.

Outcomes of Salvage Therapy for Oropharyngeal Cancer Recurrence Following Upfront Radiation Therapy and Prognostic Factors.

PURPOSE: This study aimed to investigate the oncologic outcomes and prognostic factors of salvage treatments in patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC) after radiotherapy (RT)-based treatment. MATERIALS AND METHODS: A cancer registry was used to retrieve the records of 337 patients treated with definitive RT or concurrent chemoradiotherapy (CRT) from 2008 to 2018 at a single institution. The poor-responder group (PRG) was defined as patients with residual or recurrent disease after primary treatment, and the oncologic outcomes for each salvage treatment method were analyzed. In addition, prognostic indicators of recurrence-free survival (RFS) and overall survival (OS) were identified in patients who underwent salvage treatment. RESULTS: After initial (C)RT, the PRG comprised 71 of the 337 patients (21.1%): 18 patients had residual disease, and 53 had recurrence after primary treatment (mean time to recurrence 19.5 months). Of these, 63 patients received salvage treatment (surgery 57.2%, re-(C)RT 23.8%, and chemotherapy 19.0%), and the salvage success rate was 47.6% at the last follow-up. The overall 2-year OS for salvage treatments was 56.4% (60.8% for the salvage surgery group and 46.2% for the salvage re-(C)RT). Salvage surgery patients with negative resection margins had better oncologic outcomes than those with close/positive resection margins. Using multivariate analyses, locoregional recurrence and residual disease after primary surgery were associated with poor outcome after salvage treatment. In Kaplan-Meier analyses, p16 status was significantly associated with OS in the initial treatment setting but not in the salvage setting. CONCLUSION: In recurrent OPSCC after RT-based treatment, successful salvage was achieved in 56.4% patients who had undergone salvage surgery and radiation treatment. Salvage treatment methods should be selected carefully, given recurrence site as a prognostic factor for RFS.

Improved Early Detection Models of Pharyngocutaneous Fistula after Total Laryngectomy.

Early detection of pharyngocutaneous fistula (PCF) after total laryngectomy (TL) could prevent severe complications such as major vessel rupture. We aimed to develop prediction models for detecting PCF in the early postoperative period. We retrospectively analyzed patients (N = 263) who received TL between 2004 and 2021. We collected clinical data for fever (>38.0 °C) and blood tests (WBC, CRP, albumin, Hb, neutrophils, lymphocytes) on postoperative days (POD) 3 and 7, and fistulography on POD 7. Clinical data were compared between fistula and no fistula groups, and significant factors were selected using machine learning. Using these clinical factors, we developed improved prediction models for PCF detection. Fistula occurred in 86 (32.7%) patients. Fever was significantly (p < 0.001) more common in the fistula group, and ratios (POD 7 to 3) of WBC, CRP, neutrophils, and neutrophils-to-lymphocytes (NLR) were significantly higher (all p ≤ 0.001) in the fistula group than in the no fistula group. Leakage on fistulography was more common in the fistula group (38.2%) than in the no fistula group (3.0%). The area under curve (AUC) of fistulography alone was 0.68, but predictive models using a combination of fistulography, WBC at POD 7, and neutrophil ratio (POD 7/POD 3) showed better diagnostic performance (AUC of 0.83). Our predictive models may detect PCF early and accurately, which could reduce fatal complications following PCF.

Expression of sodium-iodide symporter and TSH receptor in subclinical metastatic lymph nodes of papillary thyroid microcarcinoma.

BACKGROUND: The clinical significance of the subclinical lymph node (LN) metastasis in clinically node-negative (cN0) papillary thyroid microcarcinoma (PTMC) has been debated. We investigated the expression of sodium-iodide symporter (NIS) and thyroid-stimulating hormone receptor (TSHR) in the subclinical metastatic LNs of PTMC, which are crucial prerequisites for the response to radioactive iodine treatment. METHODS: Among 149 consecutive patients who received total thyroidectomy in conjunction with prophylactic central neck dissection for cN0 PTMC from October 2005 to December 2007, 20 who had single PTMC and subclinical LN metastasis (cN0, pN1, single PTMC) were included. Immunohistochemical staining was performed with anti-human NIS antibody and anti-human TSHR antibody in 20 primary tumors and 52 metastatic LNs. RESULTS: NIS and TSHR expression was detected in 19 (95%) and 18 (90%) of 20 PTMCs, respectively. NIS and TSHR expression were also detected in 50 (96.2%) and 39 (75%) of 52 metastatic LNs, respectively. In 85% of patients, the presence of NIS expression in primary PTMCs was concordant with that in corresponding metastatic LNs. Intensities of NIS and TSHR expression were diverse. In 6 of 12 cases of multiple metastatic LNs, the metastatic LNs showed heterogeneous intensities of NIS expression. CONCLUSIONS: The presence of NIS and TSHR expression was observed with high frequency in both PTMCs and corresponding subclinical metastatic LNs. However, the intensity of NIS and TSHR expression was diverse. Multiple metastatic LNs from single primary tumor focus could have heterogeneous intensity of NIS expression.