High-grade Salivary Gland Carcinomas Research Articles

Prognostic factors for development of distant metastases in surgically treated high-grade salivary gland carcinomas: results of retrospective single center study with 213 patients.

Distant metastases (DM) are the primary cause of treatment failure and death of patients with salivary gland carcinomas (SGC). The purpose of present study was to evaluate factors predictive on DM development in a cohort of patients with high-grade salivary gland carcinomas. This was a retrospective cohort study of consecutive patients surgically treated with curative intention at the authors' institution from January 1993 to December 2018. Outcomes evaluated were overall survival (OS), disease specific survival (DSS), recurrence free survival (RFS), locoregional recurrence free survival (LRFS) and distant metastasis free survival (DMFS). A total of 213 patients, 117 males (55%) and 96 females (45%), were included in the study. Parotid gland malignancies accounted for 56% of all cases. Adenoid cystic carcinoma (119 cases; 56%) was the most common tumor type. Cumulative OS for the 5-and 10-year follow-up period was 80% and 58% respectively. DM occurred with 75 patients (35%). The most common locations for DM were lung (55 cases; 73%) and liver (12 cases; 16%). Pathological nodal status, particularly the number of metastatic nodes, was the independent prognostic factor for OS, DSS, RFS and DMFS. Number of metastatic lymph nodes, instead of extranodal extension and largest nodal diameter, was the contributing factor related to DMFS. Since the main function of staging system is to predict outcomes, the significance of extranodal extension and nodal dimension in salivary gland cancer staging system requires further clarification. The elective neck dissection could be considered therapeutic approach for high-grade SGC since occult metastases were detected in 33% of cases.

Efficacy of Cetuximab Combined with Paclitaxel in Patients with Recurrent Salivary Gland Carcinoma: A Retrospective Observational Study

Introduction: Due to the rarity and various histological types, a standard chemotherapy regimen for recurrent or metastatic salivary gland carcinoma (SGC) has not been established. Molecular-targeted therapy is a novel cancer therapy based on the expression of target molecules. However, few molecular-targeted therapy types have shown satisfactory efficacy for patients with SGC. Our study described promising results of epidermal growth factor receptor (EGFR)-targeting therapy with paclitaxel in patients with SGC. Methods: The medical records of patients with recurrent SGC treated with weekly cetuximab combined with paclitaxel (Cmab-PTX) between December 2017 and December 2022 at our institutions were retrospectively analyzed. Results: Seven patients with SGC received Cmab-PTX therapy. The median age was 76 years. All patients were high-grade histological types, and EGFR expression was positive in all examined patients. Cmab-PTX was administered for a median period of 20 months (range of 2–36 months). The overall responses were three with complete response, two with partial response, one with stable disease (>24 weeks), and one with progressive disease. The objective response and disease control rates were 71.4% and 85.7%, respectively. Progression-free survival ranged between 2 and 36 months (median 12 months), whereas overall survival ranged between 4 and 111 months (median 36 months). One patient experienced a grade 4 adverse event (neutropenia), which was conservatively manageable. Conclusion: Although the treatment sensitivity of SGC with high-grade histological types is usually poor, Cmab-PTX could be a promising treatment regimen for recurrent SGC. Due to the rarity and various histological types, a standard chemotherapy regimen for recurrent or metastatic salivary gland carcinoma (SGC) has not been established. Molecular-targeted therapy is a novel cancer therapy based on the expression of target molecules. However, few molecular-targeted therapy types have shown satisfactory efficacy in patients with SGC. Our study described promising results of cetuximab (Cmab), epidermal growth factor receptor (EGFR)-targeting therapy with paclitaxel (PTX) in patients with SGC. Seven patients with SGC received Cmab-PTX therapy. The median age was 76 years. All patients were high-grade histological types, and EGFR expression was positive in all examined patients. Cmab-PTX was administered for a median period of 20 months. The overall responses were three with complete response, two with partial response, one with stable disease (>24 weeks), and one with progressive disease. The objective response rate was 71.4%. Progression-free survival ranged between 2 and 36 months (median 12 months), whereas overall survival ranged between 4 and 111 months (median 36 months). One patient experienced a grade 4 adverse event (neutropenia), which was conservatively manageable. Our study revealed a preferable objective response rate of Cmab-PTX for patients with high-grade SGC. Although the treatment sensitivity of SGC with high-grade histological types is usually poor, Cmab-PTX could be a promising treatment regimen for recurrent SGC.

Survival analysis of high-grade salivary gland carcinoma adjusted for length bias due to delay in comprehensive genomic profiling.

Survival analysis of high-grade salivary gland carcinoma adjusted for length bias due to delay in comprehensive genomic profiling.

CDK12 alterations and ARID1A mutations are predictors of poor prognosis and therapeutic targets in high-grade salivary gland carcinoma: analysis of the National Genomic Profiling Database.

Due to the diversity of histopathologic types in salivary gland carcinoma, genomic analysis of large cohorts with next-generation sequencing by histologic type has not been adequately performed. We analysed data from 93 patients with salivary duct carcinoma and 243 patients with adenoid cystic carcinoma who underwent comprehensive genomic profiling testing in the Center for Cancer Genomics and Advanced Therapeutics database, a Japanese national genome profiling database. We visualised gene mutation profiles using the OncoPrinter platform. Fisher's exact test, Kaplan-Meier analysis, log-rank test and Cox regression models were used for statistical analysis. In salivary duct carcinoma, a population with CDK12 and ERBB2 co-amplification was detected in 20 of 37 (54.1%) patients with ERBB2 amplification. We identified five loss-of-function variants in genes related to homologous recombination deficiency, such as BRCA2 and CDK12. Cox survival analysis showed that CDK12 and ERBB2 co-amplification is associated with overall survival (hazard ratio, 3.597; P=0.045). In salivary duct carcinoma, NOTCH1 mutations were the most common, followed by mutations in chromatin modification genes such as KMT2D, BCOR, KDM6A, ARID1A, EP300 and CREBBP. In the multivariate Cox analysis, activating NOTCH1 mutations (hazard ratio, 3.569; P=0.009) and ARID1A mutations (hazard ratio, 4.029; P=0.034) were significantly associated with overall survival. CDK12 and ERBB2 co-amplification is associated with a poor prognosis in salivary duct carcinoma. Chromatin remodelling genes are deeply involved in tumour progression in adenoid cystic carcinoma. One such gene, ARID1A, was an independent prognostic factor. In salivary duct carcinoma and adenoid cystic carcinoma, there might be minor populations with mutations that could be targeted for treatment with the synthetic lethality approach.

A phase II trial of neoadjuvant nivolumab, docetaxel, and cisplatin therapy followed by surgery and radiation therapy for resectable high-grade salivary gland carcinoma.

TPS6110 Background: Salivary gland carcinomas (SGCs) are rare entities that contribute to approximately 5% of head and neck malignancies. The current standard therapy for resectable SGC is complete surgical resection with adjuvant radiotherapy or chemoradiotherapy. However, the patients with high-grade histological subgroup tumors have the highest risk of regional and distant metastasis as the primary cause of treatment failure.. The previous evidence demonstrates that neoadjuvant chemotherapy showed a statistically significant advantage in survival for patients with head and neck cancer. Based on the success of neoadjuvant immune checkpoint inhibitors (ICI) in preventing disease recurrence and achieving pathologic complete response (pCR) in different types of cancer, we designed this study by incorporating nivolumab combined with neoadjuvant cytotoxic chemotherapy in patients with potentially resectable high-grade SGCs. Methods: This study is the phase II, open-label, single-center study of nivolumab in combination with docetaxel, and cisplatin as a neoadjuvant therapy in high-grade resectable SGCs. All the patients must be confirmed with pre-defined high-grade histology and clinically node-positive. As the representative inclusion/exclusion criteria, all the patients must not receive prior cancer therapy in advance to study enrollment, including another kind of immunotherapy, cytotoxic chemotherapy, or radiotherapy. Three cycles of nivolumab (360mg), docetaxel (60mg per m2), and cisplatin (60mg per m2) are applied every three weeks. Three weeks after the last treatment, the patient is re-evaluated for the surgery and will undergo surgery within seven weeks after the last treatment. Based on the surgical pathologic outcome, additional radiotherapy will be initiated between 4 to 8 weeks after the surgery per the following guidance; R0: 59.4Gy/25fx; R1 or R2: 59.4Gy/25fx with optional boost 6.6Gy/3fx. The primary objective is the major pathologic response rate defined by ≤ 10% of tumors composed of viable tumors. Complete resection rate, response rate, downstaging at pathologic staging, two-year distant metastasis free-survival, disease-free survival, overall survival, safety results, surgical outcomes of facial nerve function, completeness of post-neoadjuvant surgery will be analyzed as the secondary objectives. The sample size was calculated using H0 of mPR ≤25% and H1 of mPR ≥50%, according to the one-arm binomial model (power of 90% and one-sided alpha of 0.05). A total of 50 patients will be recruited, include 40 evaluable patients. This study is currently recruiting patients at Samsung Medical Center, South Korea. The first subject received treatment in Nov. 2022 and three patients received the treatment. The time point for the primary analyses is Q3.2025. (ONO-4538-X78). Clinical trial information: NCT05727410 .

Incidence and Prognostic Significance of PD-L1 Expression in High-Grade Salivary Gland Carcinoma.

ObjectivePD-L1 is one of the predictors of immunotherapy efficacy. Our goal was to analyze its expression and prognostic significance in high-grade salivary gland carcinoma (SGC).MethodsPD-L1 expression was evaluated using paraffin-embedded specimens from patients with surgically treated high-grade SGC, and it was scored by the tumor proportion score (TPS), combined positive score (CPS), and immune cell (IC) score. Associations between clinicopathological variables, disease-free survival (DFS), overall survival (OS) and PD-L1 expression were assessed.ResultsTPS≥1% occurred in 47 patients with an incidence of 43.1%, and it was significantly related to an advanced tumor stage. In patients with TPS<1%, TPS ranging from 1% to 20%, and TPS≥20%, the 5-year DFS rates were 36%, 26%, and 13%, respectively, and the difference was significant. In patients with TPS<1%, TPS ranging from 1% to 20%, and TPS≥20%, the 5-year OS rates were 49%, 24%, and 13%, respectively, and the difference was significant. CPS≥1 occurred in 87 patients with an incidence of 79.8%. IC scores of 0, 1, 2, and 3 were noted in 24 (22.0%), 37 (33.9%), 31 (28.4%), and 17 (15.6%) patients, respectively. Both CPS and IC scores had no impact on DFS or OS.ConclusionsThe expression of PD-L1 in tumor cells of high-grade SGCs was not uncommon, and it was significantly associated with tumor stage. PD-L1 expression in tumor cells rather than in immune cells indicated a poor prognosis.

Cytologic grading of primary malignant salivary gland tumors: A blinded review by an international panel.

Fine needle aspiration (FNA) is commonly used for the preoperative evaluation of salivary gland tumors. Tumor grade is a key factor influencing clinical management of salivary gland carcinomas (SGCs). To assess the ability to grade nonbasaloid SGCs in FNA specimens, an international panel of cytopathologists convened to review and score SGC cases. The study cohort included 61 cases of primary SGC from the pathology archives of 3 tertiary medical centers. Cases from 2005 to 2016 were selected, scanned, and digitized. Nineteen cytopathologists blinded to the histologic diagnosis reviewed the digitized cytology slides and graded them as low, high, or indeterminate. The panelists' results were then compared to the tumor grades based on histopathologic examination of the corresponding resection specimens. All but 2 of the 19 (89.5%) expert panelists review more than 20 salivary gland FNAs per year; 16 (84.2%) of the panelists work at academic medical centers, and 13 (68.4%) have more than 10years' experience. Participants had an overall accuracy of 89.4% in the grading of SGC cases, with 90.2% and 88.3% for low- and high-grade SGC, respectively. Acinic cell carcinoma and mucoepidermoid carcinoma had the highest degree of accuracy, while epithelial-myoepithelial carcinoma and salivary duct carcinoma had the lowest degree of accuracy. As expected, the intermediate-grade SGC cases showed the greatest variability (high-grade, 42.1%; low-grade, 37.5%, indeterminate, 20.4%). This study confirms the high accuracy of cytomorphologic grading of primary SGC by FNA as low- or high-grade. However, caution should be exercised when a grade cannot be confidently assigned.

Androgen receptor immunohistochemistry in salivary duct carcinoma: a retrospective study of 188 cases focusing on tumoral heterogeneity and temporal concordance

Salivary duct carcinoma (SDC) is a high-grade salivary gland carcinoma that is associated with frequent metastasis and poor outcome. Androgen receptor (AR) immunoexpression in SDC is reported in 69% to 100% of SDC. Androgen deprivation therapy (ADT) has shown a response rate of 18% to 42% in SDC. Therefore, AR immunoexpression may serve as a diagnostic and predictive marker for ADT response in SDC. We investigated AR immunopositivity and staining pattern in a large retrospective cohort of 188 SDCs from 163 patients, including 22 paired primary and metastatic SDCs from the same patients, focusing specifically on staining heterogeneity and concordance. A control cohort of 61 non-SDC salivary gland carcinomas was also included. AR immunopositivity defined as ≥1% of tumor cell nuclear staining was found in 94% (177/188) of SDCs, including 95% of primary tumors, 100% of regional metastases, and 90% of distant metastases. Most of the cases (75%, 86/114) showed homogeneous and diffuse AR positivity. However, a subset (25%) exhibited focal or heterogeneous AR staining pattern. Although most metastases (21/22, 95%) had concordant AR expression with the primary tumors, one treatment-naïve tumor (5%) had complete loss of AR immunoexpression in the metastasis without detectable molecular alterations in AR or AR co-regulators. AR positive staining in non-SDC salivary carcinomas was infrequent (15%, 9/61), and mostly heterogeneous or focal. AR immunoexpression is highly prevalent in SDC, in both primary (94%) and metastatic tumors (93%). The cumulative AR immunopositivity rate in SDC is 90% based on data from the current study and previous literature. A small subset may show intratumoral AR heterogeneity and discordant AR expression in metastasis. AR immunoexpression may be seen in non-SDC salivary gland carcinomas but it is uncommon and usually focal.

Pre-treatment metabolic tumor volume predicts tumor metastasis and progression in high-grade salivary gland carcinoma.

High-grade salivary gland carcinoma (SGC) shows a high rate of metastasis and post-treatment recurrence, resulting in poor patient survival. Therefore, we evaluated the utility of pre-treatment 18F-FDG PET/CT parameters in predicting metastasis, tumor progression, and survival of high-grade SGC patients. This observational study included 75 patients with previously untreated high-grade SGC who underwent pre-treatment 18F-FDG PET/CT scanning and subsequent treatment. Standardized uptake values (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured on pre-treatment 18F-FDG PET/CT. Logistic regression analysis was used to identify the relationship of these factors with metastasis. Cox proportional hazard regression analyses were used to identify associations between PET parameters and both progression-free survival (PFS) and overall survival (OS). A total of 36 (48%) patients had neck or distant metastases at initial staging. After controlling for clinical factors, MTV (> 8.8mL) was an independent factor for initial metastasis (adjusted odds ratio 4.80, 95% confidence interval 1.09-21.20; P = 0.039). All PET parameters of SUVmax (> 4.3), SUVmean (> 3.0), SUVpeak (3.9), MTV (> 8.8mL), and TLG (> 31.1g) were significant variables for PFS (all P < 0.05), while MTV and TLG were significant factors for OS. After controlling for clinicopathological factors, MTV (adjusted hazard ratio 4.36, 95% confidence interval 1.69-11.26; P = 0.002) and TLG (3.41, 1.47-7.91; P = 0.004) were significantly associated with PFS, but not OS. MTV is useful among quantitative PET measurements for predicting initial metastasis and PFS in patients with high-grade SGC.

Reproducibility of PD-L1 immunohistochemistry interpretation across various types of genitourinary and head/neck carcinomas, antibody clones, and tissue types

Programmed death-ligand 1 (PD-L1) expression by tumor cells is a mechanism for down-regulation of antitumor T-cell responses and is a target for immunotherapy in various cancers. PD-L1 status as a predictor of treatment response has led to the development of multiple platforms with different reference cutoffs. We studied 128 cases of genitourinary and head/neck carcinomas, aiming to assess the frequency of PD-L1 positivity, interobserver reliability of PD-L1 interpretation, and the concordance of PD-L1 scoring between small samples from tissue microarray and whole sections using SP263 and SP142 clones. No prostatic carcinoma (0/21) was PD-L1 positive compared with 15% to 24% PD-L1 positivity in urothelial carcinoma (UC), hypopharyngeal squamous cell carcinoma (HP-SCC), and high-grade salivary gland carcinoma. There was substantial interobserver agreement in determining overall PD-L1 positivity in UC and HP-SCC using SP263 (κ = 0.702) and SP142 (κ = 0.757) antibodies. Subgroup analysis for both antibodies showed excellent agreement in UC (κ = 0.812 and 0.827) and moderate agreement in HP-SCC (κ = 0.469 and 0.591). Moderate to substantial agreement between tissue microarray and whole sections was achieved using SP263 (overall, κ = 0.573; UC, κ = 0.424; and HP-SCC, κ = 0.667) and SP142 (UC, κ = 0.493). PD-L1 interpretation in genitourinary and head/neck carcinomas is reliable and reproducible among pathologists and across different tissue preparations. Tumor PD-L1 staining heterogeneity may lead to discrepant PD-L1 results between small biopsies and large sections from surgical resection in a subset of tumors (19% of UC and 15% of HP-SCC). Retesting in such cases may be required to determine patient suitability for anti-PD-1/PD-L1 therapy.

Consistent LEF-1 and MYB Immunohistochemical Expression in Human Papillomavirus-Related Multiphenotypic Sinonasal Carcinoma: A Potential Diagnostic Pitfall.

Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is a distinct, newly-described sinonasal tract neoplasm characterized by a salivary gland tumor-like appearance with myoepithelial and ductal cells, frequent surface squamous dysplasia, and relatively indolent behavior. When considering a diagnosis of HMSC, aggressive high-grade salivary gland carcinomas, particularly those with a basaloid morphology such as basal cell adenocarcinoma and adenoid cystic carcinoma, enter the differential diagnosis. The full morphologic and immunophenotypic profile of HMSC continues to be unraveled. In this series of ten cases, we demonstrate that this tumor has consistent, strong immunohistochemical expression of LEF-1 yet lacks nuclear expression of β-catenin, and also has consistent yet variable expression of MYB protein. While LEF-1 expression may be a useful diagnostic adjunct, it can also be a pitfall, as other salivary tumors such as basal cell adenocarcinoma have been previously shown to express LEF-1. Additionally, MYB protein expression is not a discriminatory marker when trying to separate HMSC from adenoid cystic carcinoma.

Abstract 4662: Expression of PLAG1 in salivary duct carcinomas: its efficacy of the distinction of carcinoma ex pleomorphic adenoma type and de novo type

Abstract Salivary gland duct carcinoma (SDC) is one of the high-grade salivary gland carcinoma, classified into two patterns; i) carcinoma ex pleomorphic adenoma (Ca-ex-PA) type, which is derived from benign pleomorphic adenoma (PA), ii) de novo type, which is generated from normal salivary gland tissue. According to current WHO classification, Ca-ex-PA is diagnosed when pathological examination proves as follows, a) the mixture of the component of cancer cells and that of pre-existing PA cells, b) the existence of malignant cells after the resection of PA. However, current criteria cannot entirely be accurate from the viewpoint of disease onset. For example, i) if a benign component of PA is replaced completely by Ca-ex-PA, the Ca-ex-PA type can be misdiagnosed as de novo type because histopathological examination cannot clarify the existence of PA in its surgery specimen. Moreover, ii) if a de novo type SDC, arising from normal salivary tissue, is growing and infiltrate to the preexisting PA, the de novo type can be misdiagnosed as Ca-ex-PA type. Recently, Pleomorphic adenoma gene 1 (PLAG1) has been identified as the gene associated with tumorigenesis of PA. Subsequently, the overexpression of PLAG1 protein has been reported to be observed in both PAs and Ca-ex-PAs and useful for diagnosis of them. Thus, we considered that PLAG1 immunohistochemistry can enable us to distinguish Ca-ex-PA type and de novo type in SDCs more definitively. In this study, 23 SDC patients who underwent primary surgery for cancer at our institution were enrolled, including 14 Ca-ex-PA types and 9 de novo types. In each case, we had its formalin-fixed-paraffin-embedded tissue sample stained for PLAG1-antibodies (clone 3B7, Mouse mAb, 1:100, Abnova) and evaluated PLAG1 protein expression in the component of glandular-epithelial component and that of non-glandular-epithelial, respectively. PLAG1 immunostaining was scored as positive when the more than 10% nuclear staining of tumor cells are observed. In all 23 SDCs, there was no PLAG1 protein overexpression in glandular-epithelial component, irrespective of benign or malignant. In all 14 Ca-ex-PA types, positive findings of PLAG1 overexpression were observed in non-glandular-epithelial component. In all 9 de novo types, no non-glandular-epithelial component showed any signs of PLAG1 protein overexpression. There was no discrepancy of conventional criteria and the status of PLAG1, which are the cases; i) Ca-ex-PA which is misdiagnosed as de novo type, ii) de novo type which is misdiagnosed as Ca-ex-PA type. Conclusions : There is no difference between conventional criteria and PLAG1-based criteria in our cases. However, in the cases with obscure characteristics of PA morphologically, such as mucoid/myxoid or cartilaginous-like materials, findings of PLAG1-positive cells can help us to distinguish Ca-ex-PA type from de novo type more definitively. Citation Format: Takayoshi Suzuki, Satoshi Kano, Kanako Hatanaka, Yutaka Hatanaka, Tomohiro Sakashita, Takatsugu Mizumachi, Hiromitsu Hatakeyama, Akihiro Homma, Yoshihiro Matsuno, Satoshi Fukuda. Expression of PLAG1 in salivary duct carcinomas: its efficacy of the distinction of carcinoma ex pleomorphic adenoma type and de novo type [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4662. doi:10.1158/1538-7445.AM2017-4662

Definitive Radiation Therapy as an Alternative Treatment for High-Grade Salivary Gland Carcinomas: A Propensity Score Matched Study

Definitive Radiation Therapy as an Alternative Treatment for High-Grade Salivary Gland Carcinomas: A Propensity Score Matched Study

Prognostic Value of Preoperative Metabolic Tumor Volume and Total Lesion Glycolysis Measured by 18F-FDG PET/CT in Salivary Gland Carcinomas

Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) from (18)F-FDG PET/CT are emerging prognostic biomarkers in various human cancers. This study examined the prognostic value of these metabolic tumor parameters measured by pretreatment (18)F-FDG PET/CT in patients with salivary gland carcinomas. Forty-nine patients with intermediate- or high-grade salivary gland carcinomas who underwent definitive surgery with or without radiotherapy or chemoradiotherapy were evaluated preoperatively by (18)F-FDG PET/CT. Maximum standardized uptake values (SUV max), MTV, and TLG were measured for each patient. Univariate and multivariate analyses were used to identify clinicopathologic and imaging variables associated with progression-free survival (PFS) and overall survival (OS). Univariate analyses included the following variables: age, sex, pT and pN classifications, overall pTNM stage, histologic grade, resection margin, tumor lymphovascular invasion and perineural invasion, postoperative adjuvant therapy, gross total volume, SUV max, MTV, and TLG. The 3-y PFS and OS rates for all study patients were 66.9% and 81.6%, respectively. The median SUV max, MTV, and TLG were 5.1 (range, 1.7-21.5), 16.2 mL (1.0-115.1 mL), and 24.4 g (2.1-224.4 g), respectively. Univariate analyses showed that there were significant correlations between pT classification, pN classification, MTV, and TLG and both PFS and OS (P < 0.05). However, SUV max was not associated with either PFS (P = 0.111) or OS (P = 0.316). Multivariate analyses revealed that MTV (P = 0.011; hazard ratio, 11.50; 95% confidence interval, 1.45-91.01) and TLG (P = 0.038; hazard ratio, 3.55; 95% confidence interval, 1.07-11.76) were independent variables for PFS. Pretreatment values of MTV and TLG are independent prognostic factors in patients with intermediate or high-grade salivary gland carcinomas.

Elective neck management for high-grade salivary gland carcinoma

PurposeTo determine whether patients with clinically node negative (cNo) high grade salivary gland carcinomas benefit from an elective neck dissection prior to postoperative radiotherapy (RT). Material/MethodsBetween October 1964 and October 2009, 59 previously untreated patients with cNo high-grade salivary gland carcinomas (squamous cell carcinomas were excluded) were treated with curative intent using elective neck dissection (END; n=41), or elective neck irradiation (ENI; n=18) at the University of Florida College of Medicine (Gainesville, FL). All patients underwent resection of the primary cancer followed by postoperative RT. The median follow-up period was 5.2years (range, 0.3–34years). ResultsOccult metastases were found in 18 (44%) of the 41 patients in the END group. There were 4 recurrences (10%) in the END group and 0 recurrence in the ENI group. Neck control rates at 5years were: END, 90%; ENI, 100%; and overall, 93% (p=0.1879). Cause-specific survival was 94% in the ENI group, 84% in the END group, and 86% for all patients (p=0.6998). There were 3 reported grade 3 or 4 toxicities. Two patients had a postoperative fistula and one patient had a grade 4 osteoradionecrosis that required a partial mandibulectomy. ConclusionsPatients with cNo high grade salivary gland carcinomas who are planned to undergo surgery and postoperative RT likely do not benefit from a planned neck dissection.

Elective Neck Management for High Grade Salivary Gland Carcinoma

Purpose/Objective(s)The authors analyzed the outcomes of high-grade salivary gland patients treated with elective neck dissection and postoperative radiation therapy (RT) versus elective neck irradiation in conjunction with postoperative RT.Materials/MethodsBetween October 1964 and October 2009, 65 previously untreated clinically node-negative neck patients were treated with curative intent with elective neck dissection (END; n = 43), elective neck irradiation (ENI; n = 20), or no elective neck treatment (n = 2). All patients had high-grade salivary gland tumor histology (squamous cell histology was excluded). The median follow-up period was 5.2 years (range, 0.3-34 years).ResultsOccult metastases were found in 19 (44%) of the 43 patients in the END group. There were 4 recurrences (6%) in the END group and 0 recurrences in the ENI group. Neck control was 100% in the ENI, 90% in the END group, and 93% for all patients (p=0.177). Cause-specific survival was 95% in the ENI group, 84% in the END group, and 88% for all patients (p=0.9713). Nine patients experienced grade 3 or 4 toxicities. Four patients (6%) had grade 3 mucositis requiring feeding tube placement. Three patients (5%) had fistulas from surgery. Two patients (3%) had grade 4 osteonecrosis of the jaw requiring mandibulectomy.ConclusionsElective neck management indications include high-grade histology and T3/T4 primary. Elective neck irradiation provides excellent regional control. If postoperative RT is indicated preoperatively, then elective neck dissection is unnecessary. Purpose/Objective(s)The authors analyzed the outcomes of high-grade salivary gland patients treated with elective neck dissection and postoperative radiation therapy (RT) versus elective neck irradiation in conjunction with postoperative RT. The authors analyzed the outcomes of high-grade salivary gland patients treated with elective neck dissection and postoperative radiation therapy (RT) versus elective neck irradiation in conjunction with postoperative RT. Materials/MethodsBetween October 1964 and October 2009, 65 previously untreated clinically node-negative neck patients were treated with curative intent with elective neck dissection (END; n = 43), elective neck irradiation (ENI; n = 20), or no elective neck treatment (n = 2). All patients had high-grade salivary gland tumor histology (squamous cell histology was excluded). The median follow-up period was 5.2 years (range, 0.3-34 years). Between October 1964 and October 2009, 65 previously untreated clinically node-negative neck patients were treated with curative intent with elective neck dissection (END; n = 43), elective neck irradiation (ENI; n = 20), or no elective neck treatment (n = 2). All patients had high-grade salivary gland tumor histology (squamous cell histology was excluded). The median follow-up period was 5.2 years (range, 0.3-34 years). ResultsOccult metastases were found in 19 (44%) of the 43 patients in the END group. There were 4 recurrences (6%) in the END group and 0 recurrences in the ENI group. Neck control was 100% in the ENI, 90% in the END group, and 93% for all patients (p=0.177). Cause-specific survival was 95% in the ENI group, 84% in the END group, and 88% for all patients (p=0.9713). Nine patients experienced grade 3 or 4 toxicities. Four patients (6%) had grade 3 mucositis requiring feeding tube placement. Three patients (5%) had fistulas from surgery. Two patients (3%) had grade 4 osteonecrosis of the jaw requiring mandibulectomy. Occult metastases were found in 19 (44%) of the 43 patients in the END group. There were 4 recurrences (6%) in the END group and 0 recurrences in the ENI group. Neck control was 100% in the ENI, 90% in the END group, and 93% for all patients (p=0.177). Cause-specific survival was 95% in the ENI group, 84% in the END group, and 88% for all patients (p=0.9713). Nine patients experienced grade 3 or 4 toxicities. Four patients (6%) had grade 3 mucositis requiring feeding tube placement. Three patients (5%) had fistulas from surgery. Two patients (3%) had grade 4 osteonecrosis of the jaw requiring mandibulectomy. ConclusionsElective neck management indications include high-grade histology and T3/T4 primary. Elective neck irradiation provides excellent regional control. If postoperative RT is indicated preoperatively, then elective neck dissection is unnecessary. Elective neck management indications include high-grade histology and T3/T4 primary. Elective neck irradiation provides excellent regional control. If postoperative RT is indicated preoperatively, then elective neck dissection is unnecessary.

Lymphoepithelioma-Like Carcinoma of the Salivary Gland: Is Radiotherapy Alone Adequate?

Introduction. Lymphoepithelioma-like carcinoma (LELC) of the salivary gland is a rare tumor. Currently, surgery with or without radiotherapy is the recommended treatment for all salivary gland carcinomas. However, in contrast to other high-grade salivary gland carcinomas, LELCs are considered radiosensitive. There are only a few published reports of radiotherapy alone for the treatment of salivary gland LELC. Case. We present two cases of LELC of the salivary gland. One was treated with surgery and postoperative radiotherapy, and the other was given a single cycle of chemotherapy and then radiotherapy. Currently, both patients have no evidence of disease. Conclusion. Radiotherapy as a single modality should be reevaluated. The role of systemic chemotherapy to gain systemic control should be addressed due to noteworthy metastatic disease.

Outcomes of Postoperative Concurrent Chemoradiotherapy for Locally Advanced Major Salivary Gland Carcinoma

To investigate the potential value of postoperative concurrent chemoradiation among patients with high-risk salivary gland carcinomas. Case control study based on retrospective medical record review. A tertiary care comprehensive cancer center. A total of 24 patients, 12 with major salivary gland carcinoma who were treated with postoperative concurrent chemoradiotherapy from 1998 to 2007 (chemoradiation group), and a control group of 12 patients treated with postoperative radiation alone. Overall survival, progression-free survival, toxic effects. All but 1 patient had stage III or IV disease; close or positive surgical margins were identified in 20 patients (83%). The median radiation dose was 63 Gy. In the chemoradiation group, platinum-based regimens were used in all. Treatment was well tolerated, but toxic effects, predominantly hematologic, were increased in the chemoradiation group. To date, 8 patients have died; the median overall survival was 53 months. The overall survival in the chemoradiation group was significantly better than in the radiation-alone group: 3-year survival rates were 83% and 44%, respectively (P = .05). Locally advanced or high-grade salivary gland carcinomas follow an aggressive clinical course. Based on our limited experience, postoperative chemoradiation with a platinum-based regimen seems to be effective in selected patients and warrants further investigation.

Hepatocyte growth factor and c-met immunoreactivity are associated with metastasis in high grade salivary gland carcinomas

Hepatocyte growth factor and c-met immunoreactivity are associated with metastasis in high grade salivary gland carcinomas

Role of Hepatocyte Growth Factor and c-Met Receptor in Neoplastic Conditions of Salivary Glands

Signaling via hepatocyte growth factor (HGF) and the HGF receptor, c-Met, plays important roles in human salivary glands and salivary gland tumors. Various effects of HGF, including acceleration or inhibition of cell growth, enhancement of cell motility, increase of angiogenesis, inhibition of apoptosis and induction of morphogenesis, have been demonstrated in various epithelial cells. Our recent analysis of HGF regarding saliva, salivary gland and salivary gland tumors demonstrated that: 1) HGF was basically localized in luminal cells of fetal, normal salivary glands and salivary gland tumors; 2) saliva contained HGF protein on ELISA; 3) HGF tended to be more intensely expressed in benign salivary gland tumors than in malignant salivary gland tumors; 4) HGF/c-Met signaling was associated with cell scattering and invasion into matrix in the ACC3 adenoid cystic carcinoma cell line; 5) prognosis was poor and correlated to metastasis in high-grade salivary gland carcinomas with c-Met overexpression. These profiles suggest that HGF/c-Met systems may play significant roles in differentiation or tumor progression for salivary gland tumors.