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OBJECTIVES: To investigate the ultrasound (US) characteristics of metastatic malignancies (MM) in the major salivary glands and to assess the diagnostic value of the close relationship with the glandular capsule in identifying MM. METHODS: From January 2016 and April 2022, 122 patients with major salivary gland malignancies, including 20 patients with MM and 102 patients with primary malignancies (PM) confirmed by histopathological examination, were enrolled in this study. Their clinicopathologic and US data were recorded and analyzed. The diagnostic performance of the close relationship with the glandular capsule for differentiating MM from PM was analyzed. RESULTS: The mean age of MM were older than that of PM (59.50 ± 14.57 vs. 49.96 ± 15.73, p = 0.013). Compared with PM patients, MM were associated with a higher prevalence of local pain symptoms (p = 0.007) and abnormal facial nerve function (p < 0.001). MM were also more frequently characterized by unclear borders, rough margins, irregular shapes, heterogeneous internal echos, absence of cystic areas, presence of calcifications, close relationship with the glandular capsule, and US-reported positive cervical lymph nodes (all p < 0.05). The close relationship with the glandular capsule showed to be a good indicator in distinguishing between MM and PM, with an area under the receiver operating characteristic curve of 0.863, a sensitivity of 100%, a specificity of 72.5%, and an accuracy of 92.2%. Positive and negative predictive were calculated at 41.7% and 100%, respectively. CONCLUSIONS: The US finding of a close relationship with the glandular capsule is a highly sensitive diagnostic indicator for MM. Following this finding, US-guided needle biopsy should be recommended to further confirm the diagnosis.

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Background: This study aims to retrospectively investigate the prognostic significance of the tumor microenvironment, with a focus on TILs (tumor-infiltrating lymphocytes), in relation to survival in a large cohort of patients with parotid gland cancer, and it uses the method proposed by the International TILs Working Group in breast cancer. Methods: We included a cohort of consecutive patients with biopsy-proven parotid cancer who underwent surgery between January 2010 and September 2023. A retrospective review of medical records, including surgical, pathological and follow-up reports, was performed. The density of TILs was determined according to the recommendations of the International TILs Working Group for breast cancer. Results: A weak negative correlation (p = 0.3) between TILs and time of survival and a weak positive correlation (p = 0.05) between TILs and months of survival (high TILs were correlated with longer survival in months) were identified. High TILs were weakly negatively, but not statistically significantly p (0.7), correlated with the grading of tumor; this means that high TILs were associated with low-grade tumors. Conclusions: Contrary to previous preliminary reports, this retrospective work found no statistically significant prognostic role of TILs in parotid gland malignancies. This case series represents the largest cohort ever reported in the literature and includes all malignant histological types. Future larger molecular studies may be useful in this regard.

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The survival significance of the number of positive lymph nodes in salivary gland carcinoma remains unclear. Thus, the current study aimed to determine the effect of the number of positive lymph nodes on disease-specific survival (DSS) and overall survival (OS) in cN0 mucoepidermoid carcinoma (MEC) of the major salivary gland. Patients surgically treated for MEC of the major salivary gland between 1975 and 2019 were retrospectively enrolled from the surveillance, epidemiology, and end results database. The total population was randomly divided into training and test groups (1:1). Primary outcome variables were DSS and OS. Prognostic models were constructed based on the independent prognostic factors determined using univariate and multivariate Cox analyses in the training group and were validated in the test group using C-index. A total of 3317 patients (1624 men and 1693 women) with a mean age of 55 ± 20 years were included. The number of positive lymph nodes was an independent prognostic factor for both DSS and OS, but the effect began when at least two positive lymph nodes for DSS and three positive lymph nodes for OS were found. Predictive models for DSS and OS in the training group had C-indexes of 0.873 (95% confidence interval [CI] 0.853-0.893) and 0.835 (95% CI 0.817-0.853), respectively. The validation of the test group showed C-indexes of 0.877 (95% CI 0.851-0.902) for DSS and 0.820 (95% CI 0.798-0.842) for OS. The number of positive lymph nodes was statistically associated with survival in cN0 major salivary gland MEC. The current prognostic model could provide individualized follow-up strategies for patients with high reliability.

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Mucoepidermoid carcinoma is a type of salivary gland cancer that can develop in the context of a parotid gland cyst. This type of tumor is composed of mucous, epidermoid, and intercalated cells, and usually presents as a slow-growing and painless mass. A parotid gland cyst is a condition in which a fluid-filled sac forms in the parotid gland. The tumor can be masked as it develops within the parotid cyst. A 45-year-old female patient presented with a suspect of benign neoplasm of the major salivary gland. She underwent partial right parotidectomy, which upon pathological analysis confirmed the diagnosis of mucoepidermoid microcarcinoma associated with parotid gland cysts. The patient did well and continues under regular follow-up with no further treatment.

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OBJECTIVE: To investigate adjuvant therapy indications, utilization, and associated survival disparities in major salivary gland cancer (MSGC). STUDY DESIGN: Retrospective cohort study. SETTING: The 2006 to 2017 National Cancer Database. METHODS: Patients with surgically resected MSGC were included (N = 11,398). pT3-4 classification, pN2-3 classification, lymphovascular invasion, pathologic extranodal extension (pENE), and positive surgical margin (PSM) were considered indications for adjuvant radiotherapy (aRT). pENE and PSM were considered possible indications for adjuvant chemotherapy. Multivariable logistic and Cox regression models were implemented. RESULTS: Among 6694 patients with ≥ $\ge $ 1 indication for aRT, 1906 (28.5%) received no further treatment and missed aRT. Age, race, comorbidity status, facility type, and distance to reporting facility were associated with missed aRT (P < .025). Among 4003 patients with ≥1 possible indication for adjuvant chemoradiotherapy (aCRT), 914 (22.8%) received aCRT. Patients with pENE only (38.5%) and both pENE and PSM (44.0%) received aCRT more frequently than those with PSM only (17.0%) (P < .001). Academic facility was associated with aCRT utilization (P < .05). aCRT utilization increased between 2006 and 2017 in both academic (14.8% vs 23.9%) and nonacademic (8.8% vs 13.5%) facilities (P < .05). Among 2691 patients with ≥1 indication for aRT alone, missed aRT portended poorer OS (hazard ratio [HR]: 1.61, 95% confidence interval [CI]: 1.28-2.03, P < .001). Among 4003 patients with ≥1 possible indication for aCRT, aRT alone (HR: 1.02, 95% CI: 0.89-1.18, P = .780) and aCRT were associated with similar OS. CONCLUSION: Missed aRT in MSGC occurs frequently and portends poorer OS. Further studies clarifying indications for aCRT are required.

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OBJECTIVE: To compare surgical and nonsurgical definitive treatment in cT4b major salivary gland cancer (MSGC). STUDY DESIGN: Retrospective cohort study. SETTING: The 2004 to 2019 National Cancer Database. METHODS: The NCDB was queried for patients with cT4b MSGC (N = 976). Patients undergoing definitive treatment with (1) surgical resection + adjuvant therapy, (2) radiotherapy (RT) alone, or (3) chemoradiotherapy (CRT) were included in Kaplan-Meier and Cox survival analyses. RESULTS: Of 219 patients undergoing definitive treatment, 148 (67.6%) underwent surgical resection + adjuvant therapy and 71 (32.4%) underwent RT or CRT. There were no documented mortalities within 90 days of surgical resection. Tumor diameter and nodal metastasis were associated with decreased odds of undergoing definitive treatment (P < 0.025). Patients with positive surgical margins (PSM) had higher 5-year overall survival (OS) than those undergoing definitive RT or CRT (48.5% vs 30.1%, P = 0.018) and similar 5-year OS as those with negative margins (48.5% vs 54.0%, P = 0.205). Surgical resection + adjuvant therapy (adjusted hazard ratio: 0.55, 95% confidence interval [CI]: 0.37-0.84) was associated with higher OS than definitive RT or CRT (P < 0.025). A separate cohort of 961 patients with cT4a tumors undergoing surgical resection + adjuvant therapy was created; cT4a and cT4b (hazard ratio: 1.02, 95% CI: 0.80-1.29, P = 0.896) tumors had similar OS. CONCLUSION: A minority of patients with cT4b MSGC undergo definitive treatment. Surgical resection + adjuvant therapy was safe and associated with higher OS than definitive RT or CRT, despite high rate of PSM. In the absence of clinical trial data, appropriately selected patients with cT4b MSGC may benefit from surgical resection.

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BACKGROUND: Parkinson's disease (PD) shows cardiac sympathetic denervation (SD) in 123I-metaiodobezylguanidine (MIBG) scintigraphy. Recently, SD in the major salivary glands (MSG-SD) was introduced as a possible radiological feature of PD. OBJECTIVE: To identify the clinical characteristics of patients with PD with reduced MSG and cardiac MIBG uptake (dual-SD) compared with those with reduced MSG or cardiac MIBG uptake only (single-SD). METHODS: We recruited 90 patients with PD and 30 controls and evaluated their non-motor (e.g., hyposmia, autonomic dysfunction) and motor (e.g., Movement Disorder Society-Unified Parkinson's Disease Rating Scale) features. We also assessed MIBG uptake in the MSG and heart using a quantitative semi-automatic method, and compared MIBG uptakes between PD and controls. We set cut-off values for optimal sensitivity and specificity, and compared the clinical characteristics of patients with PD between dual- and single-SD groups. RESULTS: MSG and cardiac MIBG uptakes were significantly reduced in PD. Sixty-one patients had dual-SD, 25 had single-SD, and four had non-SD. In patients with PD with normal cardiac SD, 76.5% (13/17) of whom showed abnormalities only in MSG-SD. When clinical characteristics were compared between the dual-SD and single-/non-SD groups, patients in the dual-SD group were older and had more severe hyposmia and autonomic dysfunction, except motor features. Multiple logistic regression analysis identified age as an important confounder. CONCLUSIONS: Patients with PD with dual-SD have more severe non-motor features than other patients. Autonomic dysfunction might progress independently from dopaminergic degeneration. Furthermore, our findings indicate that aging is a crucial factor in PD progression.

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OBJECTIVE: Undergoing surgery and adjuvant radiotherapy (aRT) at the same facility has been associated with higher overall survival (OS) in head and neck squamous cell carcinoma. Our study investigates whether undergoing surgery and aRT at the same academic facility is associated with higher OS in major salivary gland cancer (MSGC). METHODS: The 2006-2018 National Cancer Database was queried for patients with MSGC undergoing surgery at an academic facility and then aRT. Multivariable binary logistic and Cox proportional hazards regression models were implemented. RESULTS: Of 2801 patients satisfying inclusion criteria, 2130 (76.0%) underwent surgery and aRT at the same academic facility. Residence in a less populated area (adjusted odds ratio [aOR] 1.69, 95% confidence interval [CI] 1.16-2.45), treatment without adjuvant chemotherapy (aOR 1.97, 95% CI 1.41-2.76), and aRT duration (aOR 1.02, 95% CI 1.01-1.04) were associated with undergoing surgery and aRT at different facilities on multivariable logistic regression adjusting for patient demographics, clinicopathologic features, and adjuvant therapy (p < 0.01). Five-year OS was higher in patients undergoing surgery and aRT at the same academic facility (68.8% vs. 61.9%, p < 0.001). Undergoing surgery and aRT at different facilities remained associated with worse OS on multivariable Cox regression (aHR 1.41, 95% CI 1.10-1.81, p = 0.007). CONCLUSION: Undergoing surgery and aRT at the same academic facility is associated with higher OS in MSGC. Although undergoing surgery and aRT at the same academic facility is impractical for all patients, academic physicians should consider same-facility treatment for complex patients who would most benefit from clear multidisciplinary communication. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3620-3632, 2024.

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PURPOSE: Due to the rarity of adenoid cystic carcinoma (ACC) of the major salivary gland, there is no consensus on the extent of prophylactic neck irradiation (PNI) for patients with clinically negative lymph nodes (cN0) disease. MATERIALS AND METHODS: We conducted a retrospective analysis of all patients with ACC of the major salivary gland who received treatment at our center between January 2010 and April 2020. The primary endpoint was regional failure-free survival (RRFS). Secondary endpoints included overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival (LRFS), and acute toxicity. RESULTS: A total of 139 patients were included in the analysis. For cN0 patients, the 5-year RRFS, OS, DMFS, and LRFS were 93.2%, 90.2%, 75.7%, and 91.4%, respectively. Multivariate analysis revealed that PORT was an independent prognostic factor for RRFS and LRFS. No statistically significant differences were observed between the Level III sparing PNI group and the Standard PNI group in terms of RRFS, OS, DMFS, and LRFS. The doses delivered to the larynx and thyroid in the Level III sparing PNI group were significantly lower than those in the Standard PNI group. CONCLUSION: In patients with cN0 ACC of the major salivary gland, PNI improves regional control, and the level III nodal region sparing radiotherapy does not increase the risk of level III recurrence, while potentially reducing toxicity.

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OBJECTIVE: To investigate the effectiveness of radiotherapy and its association with second primary malignancies (SPMs) risk in major salivary gland carcinomas (MSGCs) patients. METHODS: Cohort 1 included 7274 surgically treated MSGC patients from the Surveillance, Epidemiology, and End Results database, assessing the effectiveness of radiotherapy. Cohort 2 (n = 4213) comprised patients with ≥5-year survival in Cohort 1 to study SPMs. RESULTS: Radiotherapy decreased overall survival in MSGCs patients, but improved it in high-grade MSGCs. Cumulative SPMs incidences at 25 years were 16.5% in the radiotherapy (RT) group compared to 14.5% in the non-radiotherapy (NRT) group. For second head and neck carcinomas (SHNCs), incidences were 3.4% in RT versus 1.6% in NRT. Radiotherapy increased the relative risks of tumors, particularly SHNCs (RR = 1.78). The 10-year OS rates of SHNCs after radiotherapy were significantly lower. CONCLUSION: Radiotherapy improves survival in advanced-stage MSGCs but increases the risk of developing SPMs, particularly SHNCs.

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PURPOSE: To determine the occult nodal disease rate and whether elective regional lymph node dissection (RLND) confers any 10-year overall survival (OS) in cN0 intermediate-grade mucoepidermoid carcinoma (MEC) of the parotid gland. MATERIALS & METHODS: The National Cancer Database was reviewed from 2004 to 2016 on adults with cT1-4aN0M0 intermediate-grade parotid MEC undergoing resection with/without RLND. Comparisons between patients with and without RLND were made. Occult nodal rate and 10-year overall survival (OS) were determined. RESULTS: Out of 898 included patients with cN0 intermediate grade parotid MEC undergoing elective RLND, the occult nodal rate was 7.6%. This was significantly different from low-grade (3.9%) and high-grade (25.7%) cN0 disease. When stratified by pT-classification, marginal differences were identified between low-grade and intermediate-grade tumors, whereas high-grade tumors demonstrated increased occult nodal disease with low T-stage (pT1-pT2, 20.4% vs. 5.1%) and high T-stage (pT3-pT4a, 32.1% vs. 17.6%). Patients undergoing elective RLND were more often treated at an academic facility (53.8% vs. 41.2%), had higher pT3-pT4 tumors (19.2% vs. 10.4%), and more frequently underwent total/radical parotidectomy (46.0% vs. 29.9%) with adjuvant radiation therapy (53.8% vs. 41.0%) Cox-proportional hazard modeling did not identify RLND, regardless if stratified by nodal yield or pT-classification, nor nodal positivity as significant predictors of 10-year OS. CONCLUSIONS: The occult nodal disease in intermediate-grade parotid MEC is low and similar to low-grade. Elective RLND may have a limited impact on OS, though its effect on locoregional control remains unknown. LEVEL OF EVIDENCE: III.

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OBJECTIVES: To explore the prognostic effects of previous cancer history on patients with major salivary gland cancer (SGC). SUBJECTS AND METHODS: SGC patients with (sec-SGC) and without (one-SGC) a previous cancer from the SEER database were identified. Cox proportional hazards regression (CoxPH) models were used to compare the prognosis between sec-SGC and one-SGC patients. Subgroup analyses for sec-SGC patients by gender, previous cancer types, previous cancer histology, and cancer diagnosis interval (CDI) were performed. Two CoxPH models were constructed to distinguish sec-SGC patients with different prognostic risks. RESULTS: 9098 SGC patients were enrolled. Overall, sec-SGC patients (adjusted HR [aHR] = 1.26, p < 0.001), especially those with a CDI ≤ 5 years (aHR = 1.47, p < 0.001), had worse overall survival (OS) than one-SGC patients. In subgroup analysis, only sec-SGC patients with a previous head and neck cancer who were female (aHR = 2.38, p = 0.005), with a CDI ≤ 5 years (aHR = 1.65, p = 0.007) or with a previous squamous cell carcinoma (aHR = 6.52, p < 0.001) had worse OS. Our models successfully differentiated all sec-SGC patients into high-, intermediate- and low-risk groups with different prognosis. CONCLUSIONS: Sec-SGC patients with different previous cancer types, gender, CDI and previous cancer histology had varied prognosis. The models we constructed could help differentiate the prognosis of sec-SGC patients with different risks.

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OBJECTIVE: To determine the role of surgery of the primary tumor site in the management of primary major salivary gland cancer. MATERIAL AND METHODS: The French Network of Rare Head and Neck Tumors (REFCOR) formed a steering group, which drafted a non-systematic narrative review of the literature published on Medline, and proposed recommendations. The level of adherence to the recommendations was then assessed by a rating group, according to the formal consensus method. RESULTS: Treatment of salivary gland tumor is mainly surgical. The gold standard for parotid cancer is a total parotidectomy, to obtain clear margins and remove all intraparotid lymph nodes. For low-grade tumors, partial parotidectomy with wide excision of the tumor is acceptable in the case of postoperative diagnosis on definitive histology. In the event of positive margins on definitive analysis, revision surgery should be assessed for feasibility, and performed if possible. CONCLUSION: Treatment of primary major salivary gland cancer is based on surgery with clear resection margins, as far away as possible from the tumor. The type of surgery depends on tumor location, pathologic type and extension.

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OBJECTIVE: To determine the frequency and modality of post-treatment monitoring of primary salivary gland cancer. MATERIAL AND METHODS: The French Network of Rare Head and Neck Tumors (REFCOR) formed a steering group who drafted a narrative review of the literature published on Medline and proposed recommendations. The level of adherence to the recommendations was then assessed by a rating group, according to the formal consensus method. RESULTS: Clinical monitoring should be adapted to the risk of recurrence: initially every 3 months and progressively spaced out, becoming annual after 5 years. Post-treatment head and neck and chest imaging is recommended at 3 months. Local and regional monitoring can then be carried out yearly or twice yearly with contrast-enhanced head and neck imaging. An annual chest CT scan is recommended for high-grade tumors. For lesions at high risk of late recurrence, very prolonged annual surveillance (up to 15 years) is recommended, including screening for pulmonary metastases. CONCLUSION: Given the wide range of malignant salivary gland tumors, the modalities and frequency of post-treatment monitoring must be adapted to the expected course of the disease.

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OBJECTIVE: To identify the clinical features and prognostic factors for sublingual gland carcinoma. METHODS: This was a case-control study. Patients with surgically treated sublingual gland carcinoma were retrospectively included in the Surveillance, Epidemiology and End Results database and divided into adenoid cystic carcinoma (ACC) and non-ACC groups. Primary outcome variables were disease-specific survival (DSS) and overall survival (OS). Prognostic factors for each group were analyzed using Cox models. RESULTS: We included 251 patients (115 men and 136 women). Compared with the non-ACC group, the ACC group had a larger average tumor size and received more adjuvant radiotherapy. In patients with ACC, the pathologic grade had an independent impact on DSS and OS, and patients who were undergoing adjuvant chemotherapy had worse DSS than those who were not receiving chemotherapy. In the non-ACC group, pathologic grade IV, lymph node metastasis, and adjuvant chemotherapy were associated with poor DSS and OS, and tumor extension predicted worsening DSS. CONCLUSIONS: In sublingual gland carcinoma, the pathologic grade and adjuvant chemotherapy were the most important prognostic factors, whereas lymph node metastasis had a negative impact in non-ACC patients but not in ACC patients.

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Diagnosing primary Sjögren's syndrome (pSS) is difficult due to clinical heterogeneity and the absence of non-invasive specific biomarkers. To develop non-invasive pSS diagnosis methods that integrate classic clinical indexes, major salivary gland ultrasonography (SGUS), and gene expression profiles shared by labial gland and peripheral blood, we conducted a study on a cohort of 358 subjects. We identified differentially expressed genes (DEGs) in glands and blood that were enriched in defense response to virus and type I interferon production pathways. Four upregulated DEGs common in glands and blood were identified as hub genes based on the protein-protein interaction networks. A random forest model was trained using features, including SGUS, anti-SSA/Ro60, keratoconjunctivitis sicca tests, and gene expression levels of MX1 and RSAD2. The model achieved comparable pSS diagnosis accuracy to the golden standard method based on labial gland biopsy. Our findings implicate this novel model as a promising diagnosis technique of pSS.

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OBJECTIVE: To investigate the clinicopathological, therapeutic, and survival data on pediatric major salivary gland cancers. MATERIALS AND METHODS: National Cancer Database (NCDB) query from 2004 to 2018. RESULTS: In total, 967 cases of individuals under the age of 21 were identified. Most cancers affected the parotid gland (86%). Mucoepidermoid carcinoma (41.3%) and acinic cell adenocarcinoma (33.6%) were the most common. Tumors occurred more often from age 11 to 21, and females were more affected. Histology varied by age, gender, and race. In the 0-5 age group, mucoepidermoid carcinoma and myoepithelial carcinoma/sarcoma/rhabdomyosarcoma were the most common pathologies. In patients over 5 years old, mucoepidermoid carcinoma was the most frequent tumor in boys, while acinic cell adenocarcinoma was more common in girls. African American patients had a higher incidence of mucoepidermoid carcinoma, while White patients in the 0-5 age group had a higher incidence of myoepithelial carcinoma/sarcoma/rhabdomyosarcoma tumors. Low-grade tumors were commonly diagnosed at stage I, but the 0-5 age group had a high frequency of stage IV tumors. The overall 5-year survival rate was 94.9%, with 90% for the 0-5 years age group and 96% for the 11-15 years age group. Negative margins were associated with higher 5-year survival rates in high-stage tumors (93%) compared to positive margins (80%). Submandibular malignancies had worse 5-year survival rates across all age groups. CONCLUSIONS: Major salivary gland malignancies in pediatric patients exhibit variations in histopathologic characteristics by age, gender, and race. Negative margins impact 5-year survival rates, especially in high-stage tumors.

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Key Clinical Message: The case report describes an adenoid cystic carcinoma occurring at a rare location and the diagnostic pathway. Swellings of the floor of the mouth, whether painful or without subjective symptoms and regardless of consistency, should be taken seriously. Abstract: Adenoid cystic carcinoma (ADCC) of the sublingual salivary gland only accounts for 2% of all ADCCs. In this study, we report a rare case of ADCC with sublingual salivary gland origin in a 35-year-old man and a comprehensive review of articles published over the past 62 years.

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OBJECTIVES: The optimal treatment and associated clinical outcomes for lymphoepithelial carcinoma of the major salivary gland (LECSG) are currently unclear. As such, the purpose of this study was to assess the survival rates of LECSG patients who received either upfront surgery or upfront chemoradiotherapy (CRT). MATERIALS AND METHODS: In this retrospective study, we analyzed cases of LECSG patients treated at our center from January 2010 to April 2021. The cumulative incidences of overall survival rate (OS) and locoregional failure-free survival rate (LRFFS) were evaluated using the Kaplan-Meier method. In order to balance potential risk factors between the treatment groups, we conducted propensity score matching (PSM) at a 1:1 ratio. RESULTS: The study enrolled a total of 107 patients, among whom 24 received surgery alone, 56 underwent surgery combined with postoperative radiotherapy, and 27 underwent definitive radiotherapy. The 5-year LRFFS rate and 5-year OS rate for the entire cohort were 86.6% and 84.4%, respectively. Following PSM, the 5-year LRFFS and OS rates for the upfront CRT cases were comparable to those of upfront surgery, both before and after matching. However, the upfront surgery group showed a tendency toward more de novo facial nerve injury and post-treatment facial nerve injury. CONCLUSION: The results of this study suggest that upfront CRT is as effective as upfront surgery in terms of locoregional control and overall survival for LECSG patients. Therefore, upfront CRT could be considered a viable treatment option, potentially avoiding the risks associated with surgical intervention.

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OBJECTIVES: To analyze the risk factors for synchronous lung metastases (LM) in patients with major salivary gland mucoepidermoid carcinoma (MaSG-MEC). METHODS: MaSG-MEC patients were extracted from the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2014. Descriptive statistics were used to examine the baseline characteristics of the patients. We examined the association between risk factors and synchronous LM using Chi-squared tests. The primary study outcomes were overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier survival curves were compared using the log-rank test. Hazard analysis was conducted using the Cox proportional hazards model. RESULTS: A total of 701 patients were analyzed, which including 8 patients (1.1%) with synchronous LM, and 693 patients without synchronous LM (98.9%). Lower T or N classification, and highly differentiated disease were associated with a significantly lower risk of LM and multivariate logistic regression analysis showed that lower T classification were associated with a significantly lower risk of LM (P < 0.05, respectively). Elderly Caucasian male patients with poorly differentiated disease, multiple sites of metastases and no surgical therapy to primary tumor were more likely to reduce life expectancy. CONCLUSION: By analyzing data from a large cohort, lower T or N classification and highly differentiated disease were associated with a significantly lower risk of LM. Elderly Caucasian male patients with poorly differentiated disease, multiple sites of metastases and no surgical therapy to primary tumor were more likely to reduce life expectancy. More accurate assessments of LM will be imperative for early diagnosis and treatment in patients who harbored with higher T or N classification and poorly differentiated disease.

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