Prevalence and risk factors of postoperative laryngeal edema in patients undergoing neck dissection.

PURPOSE: Postoperative laryngeal edema (PLE) is a common complication in patients undergoing head and neck surgery, leading to symptoms such as odynophagia, dysphagia, or potential airway obstruction. However, the prevalence and risk factors of PLE in patients undergoing neck dissection (ND) have not been well investigated. METHODS: A retrospective analysis was conducted in three steps. Initially, a pilot study of 50 consecutive ND patients revealed a preliminary PLE prevalence of 0.34. Then, the medical records of an additional 295 ND patients were reviewed to estimate the prevalence of PLE with a total width of 95% confidence interval (CI) of ± 5%. Finally, multivariable logistic regression analyses were performed to identify risk factors for PLE (n = 343). RESULTS: PLE occurred in 29.4% [95%CI 24.4-34.4%] of patients undergoing any type of ND, with the most common symptoms of odynophagia (75.0%) and dyspnea (11.1%). Hospital stay was just one day longer in PLE patients, responding well with short-term steroid treatment (p = 0.0057). In multivariable analyses, no significant association was found between PLE occurrence and airway management. However, body mass index and the American Society of Anesthesiologists classification correlated with PLE. More importantly, surgery for oro-hypopharynx or supraglottis tumors (odds ratio, OR = 3.019, [95%CI 1.166-7.815]) and lymph node level 2(3) ND (OR = 4.214 to 5.279, [95%CI 1.160-20.529]) were significant risk factors for PLE. CONCLUSIONS: PLE developed in approximately 30% of ND patients, causing uncomfortable symptoms. Early diagnosis and intervention of PLE in high-risk patients can improve patient care and outcomes.

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.

Pre-treatment quality of life in patients with salivary gland cancer in comparison with those of head and neck cancer patients.

INTRODUCTION: Salivary gland cancer (SGC) is a rare malignant tumor arising from the salivary glands, with a variety of clinical and biological behaviors different from head and neck cancer (HNC). Because of the rarity of SGC, there are limited data on pre-treatment quality of life (QoL). Therefore, we evaluated the pre-treatment QoL in SGC patients by stage and compared it with that of HNC patients. METHODS: From a prospective registry of HNC patients (2016-2020), we selected 225 patients with SGC, and 912 patients with oral cavity (OC) and oropharyngeal cancer (OPC) who were diagnosed in the same period as the HNC control group. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and HNC-Specific Module (H&N35) were used to assess QoL. RESULTS: SGC patients had a statistically better baseline QoL (69.8 vs. 64.0), emotional (82.1 vs. 78.8), cognitive (92.0 vs. 88.7), and social function (86.3 vs. 80.5), and fewer symptoms than HNC patients. The estimated average QoL differences between SGC patient diagnosed at stages I and IV was -12.9. Especially, advanced-stage of tumors was associated with much lower role functioning and emotional functioning scores in SGC patients, compared to those in HNC patients, among females and of younger age. DISCUSSION: Although the overall QoL score was higher in SGC patients than in HNC patients, specific domains were significantly affected in SGC patients according to the tumor stage. Females and those of younger age were more affected by severity of disease in SGC. STUDY REGISTRATION: ClinicalTrials.gov Identifier NCT02546895.

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.

Tumor dimension-dependent microscopic extensions of hypopharyngeal cancer: Therapeutic implications for larynx-preserving hypopharyngectomy.

INTRODUCTION: Hypopharyngeal cancer (HPC) is well characterized by the early submucosal spread of cancer cells into adjacent subsites of the hypopharynx and deep tissues, advocating a wide extent of treatment. However, the microscopic extensions (ME) from gross tumors, according to the primary tumor dimensions, has not been reported in detail. METHODS: We included patients who underwent upfront curative surgery, and retrospectively reviewed pathology specimens from 45 HPC cases. The distance of the MEs, defined as tumor infiltration beyond the gross tumor border on the submucosal and deep sides, was measured. We analyzed potential correlations between MEs and various physical tumor factors. RESULTS: A rough linear correlation between the submucosal ME and the maximal diameter of tumors was found (p < .001, r2 = 0.225). Deep MEs did not correlate with tumor physical factors. However, the MEs differed significantly by the T status (p = .033 and .015 in submucosal and deep sides). In T1-2 tumors, the submucosal MEs were less than 0.5 cm, whereas those of T3-4 tumors were 1.5-2.0 cm. CONCLUSION: In HPC, local MEs beyond the gross tumor border correlated with primary tumor T status. Our findings support that the surgical safety margin for HPC can be adjusted according to tumor dimension.

Three-dimensional double-echo steady-state with water excitation magnetic resonance imaging to localize the intraparotid facial nerve in patients with deep-seated parotid tumors.

PURPOSE: To assess the utility of three-dimensional double-echo steady-state with water excitation (3D-DESS-WE) imaging for localizing deep-seated parotid tumors in relation to the facial nerve. METHODS: A prospective study comparing the surgical outcomes of parotidectomy with or without 3D-DESS-WE sequence is currently enrolling the patients. Magnetic resonance imaging data from the first 25 patients with 3D-DESS-WE sequence were reviewed. Visibility of the intraparotid facial nerve was independently assessed by two neuroradiologists. The diagnostic performance of the 3D-DESS-WE sequence for prediction of deep lobe involvement was compared with that of two conventional methods based on the retromandibular vein line (RMVL) and facial nerve line (FNL). The relationship between the tumor and the main trunk of the facial nerve was also evaluated on the 3D-DESS-WE sequence. RESULTS: On 3D-DESS-WE images, the main trunk, temporofacial division, and cervicofacial division of the intraparotid facial nerve were visualized in 100% (25/25), 48% (12/25), and 36% (9/25) of patients, respectively. The diagnostic accuracy of the 3D-DESS-WE sequence for prediction of deep lobe involvement was 92% (23/25), which was significantly superior to that of the RMVL (68% [17/25]; p = 0.008) and FNL (64% [16/25]; p = 0.004) methods. The relationship between the tumor and the main trunk of the facial nerve was correctly predicted in 92% (23/25) of 3D-DESS-WE images. CONCLUSION: By direct visualization of the facial nerve, the 3D-DESS-WE sequence improved the preoperative localization of the intraparotid facial nerve in deep-seated parotid tumors. This information may help better surgical planning for deep-seated parotid tumors.

Benefits of the Multidisciplinary Approach After Curative Surgery for the Treatment of Scalp Angiosarcoma.

BACKGROUND: Patients with scalp angiosarcoma still present with a dismal prognosis, indicating the need for a multidisciplinary approach. The present study aimed to investigate the treatment outcomes of scalp angiosarcoma with a focus on the effect of radiotherapy and chemotherapy, performed in either an adjuvant or palliative setting, after curative surgical treatment. METHODS: Patients with scalp angiosarcoma without evidence of systemic metastasis who were treated with curative ablative surgery between 2008 and 2018 were assessed. Oncologic outcomes, including recurrence-free survival (RFS) and overall survival (OS), were evaluated. RESULTS: A total of 23 patients were analyzed. All patients underwent radical resection, most of whom (82.6%) achieved R0 resection. Adjuvant radiotherapy and chemotherapy (all taxane-based) were delivered for 11 and 3 patients, respectively. Recurrence developed in 17 (73.9%) of 23 patients during a mean follow-up period of 18.4 months. The overall 2-year RFS and OS were 15.5% and 44.4%, respectively. Multivariate analysis showed that adjuvant radiotherapy and chemotherapy were associated with a significantly low risk of recurrence. In 17 patients with recurrence, those receiving palliative radiotherapy or chemotherapy had significantly higher OS than those not receiving any treatments. Compared with patients treated during the first half of the study period, those treated during the latter part, who received adjuvant and palliative radiotherapy or chemotherapy more frequently, had significantly favorable OS, with a 2-year OS of 77.8%. CONCLUSIONS: A multidisciplinary approach using radiotherapy and/or chemotherapy combined with curative resection might be associated with better oncologic outcomes in patients with scalp angiosarcoma.

Regional Lymph Node Metastasis of Scalp Angiosarcoma: A Detailed Clinical Observation Study of 40 Cases.

BACKGROUND: The incidence of lymph node metastasis (LNM) of angiosarcomas is reported to be less than 15%, and elective neck management has not been indicated. This study evaluated the incidence and pattern of regional LNM in patients with scalp angiosarcomas using the clinical data of its full course to understand time-event sequences of scalp angiosarcomas. METHODS: This retrospective study included all consecutive cases of pathology-confirmed angiosarcomas and analyzed 40 cases of scalp angiosarcomas. The survival plots were estimated using the Kaplan-Meier method, and the results are presented mainly in a descriptive manner. RESULTS: The overall survival rate for the patients was 35.8% at 2 years. In contrast to previous reports, regional LNM was observed in more than half of the patients (52.5%) with scalp angiosarcoma. Meanwhile, a direct spread to distant organs occurred in only 27.5% of the patients. Regional LNM could predict clinical manifestation of systemic disease within 3 to 6 months. No differences in survival rates between patients with and without LNM were observed in this series. Occurrence of LNM seemed to be correlated with a high mitotic rate of primary tumors, but not with tumor grade or tumor dimension. The first-echelon lymph nodes from scalp angiosarcoma were peri-parotid, post-auricular, and level 2 lymph nodes. CONCLUSIONS: For a localized scalp angiosarcoma, it seems reasonable for initial curative surgery to include prophylactic evaluation of regional lymph nodes for pathologic nodal staging, prognosis estimation, and the decision for systemic treatments.

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.

Risk of high-grade malignancy in parotid gland tumors as classified by the Milan System for Reporting Salivary Gland Cytopathology.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (Milan System) has previously shown its diagnostic utility by categorizing the seven cytology findings in salivary gland lesions. However, there has been lack of study about the risk of high-grade malignancy in the cytology diagnosis based on the Milan System. Thus, we tried to identify the diagnostic ability of the Milan System for high-grade malignancy and to suggest an improved diagnostic approach for preoperative estimation of high-grade malignancy using the Milan System. METHODS: A total of 413 patients with parotid gland tumors, who had undergone surgical resection from 2011 to 2015 were included in the present study retrospectively. Cytopathology was reclassified according to the Milan System by two independent reviewers. The outcomes were risk of malignancy and risk of high-grade malignancy. The diagnostic performance of the Milan System category [Malignant] for detecting high-grade malignancy was calculated. RESULTS: The risk of malignancy was 83.3% and 100% in the Milan System categories [Suspicious for Malignancy] and [Malignant], respectively. Meanwhile, the risk of high-grade malignancy was 16.7% and 55.9% in these two categories. Disease-free survival of patients with high-grade malignancy was significantly worse than those with low- and intermediate-grade malignancy. Union combining the Milan System category [Malignant] with the presence of nodal metastasis suggested high-grade malignancy with an acceptable diagnostic sensitivity (0.889-0.963) and negative predictive value (0.900-0.966). CONCLUSIONS: The Milan System category [Malignant] with the presence of nodal metastasis suggested parotid gland tumors as high-grade malignancy in a pretreatment setting.

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.

Optimal cutoff of pretreatment neutrophil-to-lymphocyte ratio in head and neck cancer patients: a meta-analysis and validation study.

BACKGROUND: The prognostic role of neutrophil-to-lymphocyte ratio (NLR) has been proposed in head and neck squamous cell carcinoma (HNSCC). However, it is currently unclear which cutoff values of NLR could consistently and independently differentiate HNSCC patients to better and worse prognosis groups. METHODS: We performed a meta-analysis of prognostic significance of pretreatment NLR values, using data extracted from 24 relevant articles. Main outcomes were overall survival (OS) and disease-free survival (DFS) in HNSCC patients. Pooled hazard ratio (HR) and 95% confidence intervals (95%CI) were calculated using the random effect model for outcomes. Impacts of NLR cutoff values across the studies were assessed with a meta-regression analysis. Results were validated using an independent data set of patients (n = 540). RESULTS: Pretreatment high NLR values above the cutoff were significantly associated with shorter OS (HR = 1.96, 95%CI = 1.66-2.31) and DFS (HR = 1.90, 95%CI = 1.41-2.54). Of note, NLR cutoffs ranging from 1.9 to 6.0 did not affect HR of OS or DFS in meta-regression analyses. In an independent cohort, any NLR cutoff between 2 and 6 produced significant HR of OS, similarly. Instead of binary cutoffs, three subgroups of NLR (< 2, 2 to 6, and ≥ 6) showed significant differences of OS in survival analyses. CONCLUSIONS: Meta-analyses confirmed that pretreatment NLR values above the cutoff were associated with shorter survival in HNSCC patients. However, the binary cutoffs of NLR values were variable across studies. Rather, pretreatment NLR values below 2 and above 6 using a three-tier classification (< 2, 2 to 6, and ≥ 6) could consistently imply better and worse prognosis in HNSCC patients, which could be readily translated to clinics.

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.

Postoperative anti-PD-1 antibody treatment to reduce recurrence in a cancer ablation surgical wound.

BACKGROUND: Postoperative radiation and chemotherapy are routinely applied for microscopic residual diseases; however, treatment outcomes are not optimal, and patients frequently suffer from treatment-related toxicities. To search for an effective and less-toxic adjuvant treatment for patients with high risk of recurrence, the preventive effect of anti-programmed cell death protein 1 (PD-1) treatment was evaluated in an in vivo animal model of post-surgical tumor recurrence. MATERIALS AND METHODS: An animal model of postsurgical tumor recurrence (SCCVII tumors in C3H mice) was established by reinoculating tumor cells (105 cells) into surgical wound of primary tumor resection. Initial and recurrent tumors were compared by an immunohistochemistry and complementary DNA microarray. Using this in vivo model, tumor recurrence rates were evaluated in the animals receiving anti-PD-1 treatments. Animals were rechallenged with tumor cells, and interferon gamma secretion from spleen cells was analyzed to determine tumor-specific antitumor immunity. RESULTS: FoxP3high cell population was significantly elevated in recurrent tumors compared with that in primary tumors. Some immune response-related factors (granzyme F, neuronal leucine-rich repeat protein 1, myosin heavy chain 3, and transmembrane protein 8C) showed significant differences between primary and recurrent tumors. In this animal model, anti-PD-1 treatments significantly suppressed tumor recurrence. Importantly, tumor induction was significantly reduced when anti-PD-1-treated mice were rechallenged with tumor cells. Tumor cell-specific interferon gamma production was increased in these animals. CONCLUSIONS: Postoperative anti-PD-1 treatment significantly reduced recurrence in a cancer ablation surgical wound in an in vivo model of tumor recurrence. Our data lay the preclinical groundwork for the future clinical validation of adjuvant anti-PD-1 treatments in patients.

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.

Comparison of Oncological and Functional Outcomes between Initial Surgical versus Non-Surgical Treatments for Hypopharyngeal Cancer.

BACKGROUND: Whether to administer surgical or non-surgical treatments (radiation or chemoradiation therapies) for the initial management of hypopharyngeal cancer (HPC) remains a topic of debate. Herein, we explored the differences between the two approaches in terms of oncological and functional outcomes in 332 HPC patients. METHODS: The primary endpoint was survival probability; secondary outcomes included post-treatment speech and swallowing functions and necessity of additional surgical procedures for salvage or complication management. Cox proportional hazard models using clinical variables were constructed to identify significant factors. RESULTS: The 2- and 5-year overall survival (OS) rates in all patients were 64.9 and 40.9 %, respectively. In early-stage HPC patients (N = 52), initial surgery ± radiation therapy (RT) or RT alone yielded similar oncological (60 % 5-year OS rate) and functional outcomes. As for resectable advanced-stage cancers (N = 177), initial surgery ± RT/chemoradiation therapy (SRC) and initial concurrent chemoradiation therapy (iCRT) resulted in similar 45-50 % 5-year OS rates. After sacrificing the larynx, 60 % of SRC patients recovered their speaking ability through voice prosthesis, which was less than the rate for iCRT patients (76.6 %; p = 0.008). Additional surgical interventions were required in 28.0-28.6 % of patients in both groups; however, 60 % of patients undergoing additional surgery in the iCRT group received multiple (two or more) surgical interventions (p = 0.029). CONCLUSIONS: Our data revealed similar oncological outcomes, but different functional outcomes, between initial surgical and non-surgical treatments for HPC. In resectable advanced-stage HPC, iCRT resulted in better verbal communication outcomes than SRC; however, more iCRT patients required multiple surgical interventions during clinical courses.

Low-Grade Salivary Gland Cancers: Treatment Outcomes, Extent of Surgery and Indications for Postoperative Adjuvant Radiation Therapy.

BACKGROUND: Histologic grade of tumor is one of the major prognostic predictors for patients with salivary gland cancer. Because of disease rarity, little is known about the optimal treatment modalities and outcomes in low-grade salivary gland cancers (LGSGC). We tried to identify prognostic factors, and the adequate treatment modalities and outcomes in pathologically confirmed LGSGC patients. METHODS: We retrospectively extracted the clinical and pathology data from 179 LGSGC cases from 1995 to 2013. Pathological features, such as extraparenchymal extension, perineural/nerve invasion, lymphovascular invasion/tumor emboli, and resection margin status were redefined for each case. Risk factors for recurrence, extent of surgery, and the role of postoperative radiation therapy were analyzed. RESULTS: Recurrence-free survival and overall survival were 89.6 and 96.6 % at 10 years, respectively. The presence of regional nodal metastasis and positive cancer cells at resection margin were significant unfavorable prognostic factors. Postoperative adjuvant radiation treatment significantly reduced recurrences, particularly in cases with pathology risk factors (perineural invasion, lymphovascular invasion, extraparenchymal extension, or cancer cells at the resection margin), node metastasis, and advanced T-stage tumors. Close surgical margin <5 mm was not a significant risk factor for recurrence, and less-than-total resection of the affected gland did not increase recurrence, if surgery could achieve a cancer cell-free surgical margin. CONCLUSION: Postoperative radiation clearly benefitted patients with pathology risk factors, node metastasis, and advanced T stage in LGSGC. Meanwhile, the oncological outcomes are very good with surgery alone in cases of pT1-2N0 LGSGC without pathology risk factors.

Prognostic significance of clinical and 18 F-FDG PET/CT parameters for post-distant metastasis survival in head and neck squamous cell carcinoma patients.

INTRODUCTION: Distant metastasis (M1) to vital organs remains a major cause of death in patients with head and neck squamous cell carcinomas (HNSCC). Clinically the survival periods vary in individual M1 HNSCC patients and a prognostic indicator has not been fully studied. Here, we evaluated the prognostic factors for survival including 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) parameters in M1 HNSCC patients. METHODS: The study included 108 patients with newly diagnosed M1 HNSCC (68 during clinical courses, 40 at presentation) who underwent FDG PET/CT. Maximum standardized uptake value (SUVmax) of metastatic tumors was measured by FDG PET/CT. Associations of primary tumor or metastatic tumor variables with overall survival were assessed with Cox regression models. RESULTS: Multivariate analyses demonstrated that nasopharynx primary and incomplete response of loco-regional disease to treatment were significant prognostic factors. In addition, adverse prognostic factors included short distant metastasis-free period (<10 months), high number (≥5), and high PET SUVmax (≥6.3) of metastatic lesions. The patients with at least one of these adverse features had a median survival <14 months. CONCLUSION: PET SUVmax of the metastatic tumors in M1 HNSCC patients can be a good predictor for survival. J. Surg. Oncol. 2016;114:888-894. © 2016 2016 Wiley Periodicals, Inc.