Chemoradiotherapy versus radiotherapy in high risk salivary gland cancer.

OBJECTIVE: The aim of this study was to investigate the potential survival benefits associated with chemoradiotherapy (CRT) as opposed to radiotherapy (RT) in patients with resected high-risk salivary gland cancer (SGC), with a specific focus on determining whether these benefits are influenced by the number of high-risk variables. METHODS: Patients who underwent surgical treatment for high-risk SGC were retrospectively enrolled and categorized into either CRT or RT groups. The impact of adjuvant therapy on locoregional control (LRC) and overall survival (OS) was assessed using a multivariable Cox model. RESULTS: A total of 152 patients were included following propensity score-matching. In comparison to RT, CRT did not demonstrate a significant survival advantage in terms of LRC (p = 0.485, HR: 1.14, 95%CI: 0.36-4.22) and OS (p = 0.367, HR: 0.99, 95%CI: 0.17-3.87) in entire population. But among patients with T3/4 stage, high-grade tumors, and 5 or more positive lymph nodes, the addition of chemotherapy to RT significantly (p = 0.042) correlated with a 15% reduction in the risk of cancer recurrence (95%CI: 4-54%). Conversely, in other subgroups with varying combinations of high-risk variables, CRT did not provide additional survival benefits for LRC and OS compared to RT. CONCLUSION: Adjuvant chemotherapy may be considered in conjunction with RT specifically in cases where there is a presence of T3/4 stage, high-grade tumors, and 5 or more metastatic lymph nodes in high-risk SGC.

Impact of childhood/adolescent cancer history on prognosis in parotid mucoepidermoid carcinoma.

Our goal was to assess the impact of childhood/adolescent cancer history on overall survival (OS) and disease-specific survival (DSS) in patients with parotid mucoepidermoid carcinoma (MEC). Patients who underwent surgical treatment for primary parotid MEC and those with a second malignancy of parotid MEC were retrospectively identified from the Surveillance, Epidemiology, and End Results (SEER) database. The primary outcome variables were OS and DSS. The hazard ratios (HRs) of these survival rates associated with cancer history were analysed using Cox regression models. In total, 2681 patients were included, 263 of whom had a second malignancy. The 10-year OS rates in the primary (72%) and second malignancy groups (59%) were significantly different. Cox regression confirmed that a history of cancer tended to decrease OS (p = 0.062, HR: 1.28, 95% confidence interval: 0.99 to 1.64). Subgroup analyses showed that a history of solid tumour as opposed to haematological cancer predicted worse OS, with central nervous system tumours exhibiting a more significant influence than others (p = 0.030 vs p = 0.088). Cancer history was not related to DSS. A history of childhood/adolescent cancer negatively influenced the prognosis of patients with parotid MEC, and this effect was primarily driven by a history of solid malignancy.

Molecular characterization of the salivary adenoid cystic carcinoma immune landscape by anatomic subsites.

Adenoid cystic carcinoma (AdCC) is a slow-growing salivary gland malignancy that relapses frequently. AdCCs of the submandibular gland exhibit unique differences in prognosis and treatment response to adjuvant radiotherapy compared to other sites, yet the role of tumor anatomic subsite on gene expression and tumor immune microenvironment (TIME) composition remains unclear. We used 87 samples, including 48 samples (27 AdCC and 21 normal salivary gland tissue samples) from 4 publicly available AdCC RNA sequencing datasets, a validation set of 33 minor gland AdCCs, and 39 samples from an in-house cohort (30 AdCC and 9 normal salivary gland samples). RNA sequencing data were used for single sample gene set enrichment analysis and TIME deconvolution. Quantitative PCR and multiplex immunofluorescence were performed on the in-house cohort. Wilcoxon rank-sum, nonparametric equality-of-medians tests and linear regression models were used to evaluate tumor subsite differences. AdCCs of different anatomic subsites including parotid, submandibular, sublingual, and minor salivary glands differed with respect to expression of several key tumorigenic pathways. Among the three major salivary glands, the reactive oxygen species (ROS)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway signature was significantly underexpressed in AdCC of submandibular compared to parotid and sublingual glands while this association was not observed among normal glands. Additionally, the NRF2 pathway, whose expression was associated with favorable overall survival, was overexpressed in AdCCs of parotid gland compared to minor and submandibular glands. The TIME deconvolution identified differences in CD4+ T cell populations between AdCC of major and minor glands and natural killer (NK) cells among AdCC of minor, submandibular, and parotid glands while plasma cells were enriched in normal submandibular glands compared to other normal gland controls. Our data reveal key molecular differences in AdCC of different anatomic subsites. The ROS and NRF2 pathways are underexpressed in submandibular and minor AdCCs compared to parotid gland AdCCs, and NRF2 pathway expression is associated with favorable overall survival. The CD4+ T, NK, and plasma cell populations also vary by tumor subsites, suggesting that the observed submandibular AdCC tumor-intrinsic pathway differences may be responsible for influencing the TIME composition and survival differences.

Timing of postoperative radiation therapy for major salivary gland cancers.

BACKGROUND: The impact of timing of PORT initiation for major salivary gland cancers on survival is unknown. We aim to examine the impact of PORT timeliness on overall survival (OS) of patients with major salivary gland cancers. METHODS: This was a cross-sectional analysis using data from the National Cancer Database (2004-2017) and included patients with major salivary gland cancer treated with surgery and PORT. RESULTS: In total, 5701 patients were included (3133 [55%] male, 4644 [82%] white, mean age 59 ± 16 years). For the overall cohort, PORT >6 weeks was not associated with decreased OS (1.00 aHR, 95% CI 0.89-1.11). When specifically examining patients with mucoepidermoid carcinoma, PORT >6 weeks was associated with a decreased OS (1.27 aHR, 95% CI 1.01-1.58). CONCLUSIONS: Overall, this analysis did not demonstrate a survival benefit for initiating PORT within 6 weeks for patients with salivary gland malignancies. Subset analysis did support initiating PORT within 6 weeks after resection for patients with mucoepidermoid carcinomas. This was not demonstrated in other major salivary gland cancer histologies.

Facility Volume and Changing Facilities for Postoperative Radiotherapy in Salivary Gland Cancer.

OBJECTIVES: Changing location of postoperative radiotherapy (PORT) after treatment at a high-volume facility (HVF) is associated with worse survival in various head and neck cancers. Our study investigates this relationship in salivary gland cancer (SGC). METHODS: The 2004-2016 National Cancer Database was queried for all cases of adult SGC treated with surgery and PORT with or without adjuvant chemotherapy. Patients with multiple cancer diagnoses, metastatic disease, or unknown PORT facility were excluded. Reporting facilities with >95th percentile annual case volume were classified as HVFs, the remainder were classified low-volume facilities (LVFs). RESULTS: A total of 7885 patients met inclusion criteria, of which 418 (5.3%) were treated at an HVF. Patients treated at an HVF had higher rates clinical nodal positivity (18.2% vs. 14.0%, p < 0.001) and clinical T3/T4 (27.3% vs. 20.7%, p = 0.001) disease. Patients at HVFs changed facility for PORT at lower rates (18.9% vs. 24.5%, p = 0.009). Patients treated at an HVF had higher 5-year overall survival (5-OS) than those treated at an LVF (79.0% vs. 72.0%, p = 0.042). Patients treated at an HVF that changed PORT facility had worse 5-OS (60.8% vs. 83.2%, p < 0.001). Radiation facility change was an independent predictor of worse survival in patients treated at an HVF (HR: 8.99 [3.15-25.67], p < 0.001) but not for patients treated at a LVF (HR: 1.11 [0.98-1.25], p = 0.109). CONCLUSIONS: Patients treated at an HVF changing facility for PORT for SGC experience worse survival. Our data suggest patients treated surgically at an HVF should be counseled to continue their PORT at the same institution. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Interleukin-10 induces TNF-driven apoptosis and ROS production in salivary gland cancer cells.

Treatment resistance after chemo-/immunotherapy occurs in patients with head and neck squamous cell cancers (HNSCs), including salivary gland cancers (SGCs). Interleukin-10 (IL-10), a cytokine with pro- and anti-cancer effects, has an unclear impact on HNSC/SGC cells. We show that HNSC patients exhibiting high expression of IL-10 and its receptor IL-10Rα experience have prolonged overall survival. Immunoreactive IL-10 was low in ductal cells of human SGC biopsies. Human (A253) and murine WR21-SGC cells expressed IL-10Rß, but only A253 cells expressed IL-10 and IL-10Rα. The addition of recombinant IL-10 impaired SGC cell proliferation and induced apoptosis in vitro. N-acetylcysteine restored IL-10-induced reactive oxygen species (ROS) production but did not prevent IL-10-mediated viability loss. Mechanistically, recIL-10 delayed cell cycle progression from G0/G1 to the S phase with cyclin D downregulation and upregulation of NF-kB. IL-10 increased tumor necrosis factor-α (TNF-α) in A253 and WR21 and FasL in WR21 cells. Neutralizing antibodies against TNF-α and NF-kB inhibition restored SGC proliferation after IL-10 treatment, emphasizing the critical role of TNF-α and NF-kB in IL-10-mediated anti-tumor effects. These findings underscore the potential of IL-10 to impede SGC cell growth through apoptosis induction, unraveling potential therapeutic targets for intervention in salivary gland carcinomas.

Adenoid Cystic carcinoma of minor salivary glands (AdCCmSG): a multidisciplinary update.

INTRODUCTION: Adenoid cystic carcinoma of minor salivary glands (AdCCmSG) represents a 'rarity in the rarity,' posing a clinical challenge in lack of standardized, evidence-based recommendations. At present, AdCCmSG management is mostly translated from major salivary gland cancers (MSGCs). Ideally, AdCCmSG diagnostic-therapeutic workup should be discussed and carried out within a multidisciplinary, high-expertise setting, including pathologists, surgeons, radiation oncologists and medical oncologists. AREAS COVERED: The present review provides an overview of epidemiology and pathologic classification. Moreover, the most recent, clinically relevant updates in the treatment of AdCCmSG (Pubmed searches, specific guidelines) are critically discussed, aiming to a better understanding of this rare pathologic entity, potentially optimizing the care process, and offering a starting point for reflection on future therapeutic developments. EXPERT OPINION: The management of rare cancers is often hindered by limited data and clinical trials, lack of evidence-based guidelines, and hardly represented disease heterogeneity, which cannot be successfully tackled with a 'one-size-fits-all' approach. Our goal is to address these potential pitfalls, providing an easy-to-use, updated, multidisciplinary collection of expert opinions concerning AdCCmSG management as of today's clinical practice. We will also cover the most promising future perspectives, based on the potential therapeutic targets highlighted within AdCCmSG's molecular background.

Appraisal of clinical practice guidelines for salivary gland cancer management utilizing AGREE II instrument.

OBJECTIVE: Salivary gland cancers (SGC) are rare neoplasms which comprise 1-5 % of all head and neck cancers. SGCs can be managed by resection, radiosurgery, chemotherapy, or a combination of these. Our team appraised the quality of clinical practice guidelines (CPGs) for SGC treatment and management using the Appraisal of Guidelines for Research and Evaluation (AGREE-II) instrument. DATA SOURCES: PubMed, Scopus, & EMBASE were reviewed for CPGs regarding SGC management from database inception to January 1st, 2023. REVIEW METHODS: The AGREE-II instrument was used by 4 reviewers to independently evaluate guidelines. Domain scores were generated with a satisfactory threshold being >60 % - a "high" quality CPG required >4 satisfactory domains. Intraclass correlation coefficients (ICCs) were used, via R 4.2.1., to determine inter-reviewer variability. RESULTS: Literature review identified 645 articles, with six being included after applying inclusion and exclusion criteria. Of the six included articles, one CPG was "high" quality and 5 were "low" quality. The domains with the highest scores were "Editorial Independence" (72.57 ± 36.60) and "Clarity and Presentation" (63.19 ± 26.08), while the lowest were "Rigor of Development" (34.03 ± 30.63) and "Applicability" (30.21 ± 30.46). ICC scores for each domain ranged from 0.937 to 0.983, indicating a high level of inter-rater agreement. CONCLUSION: This study found that most CPGs for the treatment and management of SGC were of "low" quality, with only one guideline being considered "high" quality based on the standard set by the AGREE-II instrument. These findings indicate that there is a high level of variability and little standardization when it comes to the quality of CPGs.

Oncologic outcomes of the most prevalent major salivary gland cancers: retrospective cohort study from single center.

BACKGROUND: The preoperative diagnosis of salivary gland cancer (SGC) is crucial for the application of appropriate treatment, particularly involving the extension of the resection. METHODS: Retrospective search of medical database identified 116 patients treated surgically with malignant tumors of salivary gland between 2010 and 2020. Analysis included the demographical data, clinical course, type of surgical and adjuvant treatment, histology type and margin status, perivascular invasion (LVI), perineural invasion (PNI), metastatic lymph nodes (LN). Facial nerve function, recurrence-free and overall survival were evaluated. Adequate statistics were used for data analysis. RESULTS: The final cohort included 63 SGC patients, with adenoid cystic carcinoma the most common pathological type (27%, n = 17), followed by adenocarcinoma (17.4% n = 11). T1 and T2 patients accounted for majority cases (n = 46). The lymph node metastases were confirmed with the histopathology in 31.7% (n = 20). Distant metastases were observed in 4.8% of cases (n = 3). 38% (n = 24) of SGC were treated selectively with surgery, 49.2% (n = 31) had postoperative radiotherapy and 15.9% (n = 10)-radio-chemotherapy. The final facial nerve function was impaired in 38% of patients. Mean overall survival (OS) for all patients was 108.7 (± 132.1) months, and was the most favorable for acinar cell carcinoma (118.9 ± 45.4) and the poorest for squamous cell carcinoma (44 ± 32). Cox regression analysis of disease-free survival and OS identified significant association only with patients' age over 65 years, the hazard ratio of 7.955 and 6.486, respectively. CONCLUSIONS: The efficacy of treatment modalities for SGC should be verified with regard to the histopathological type, but also the patients' age should be taken into account.

Assessing social vulnerabilities of salivary gland cancer care, prognosis, and treatment in the United States.

BACKGROUND: Salivary gland cancers (SGC)-social determinants of health (SDoH) investigations are limited by narrow scopes of SGC-types and SDoH. This Social Vulnerability Index (SVI)-study hypothesized that socioeconomic status (SES) most contributed to SDoH-associated SGC-disparities. METHODS: Retrospective cohort of 24 775 SGCs assessed SES, minority-language status (ML), household composition (HH), housing-transportation (HT), and composite-SDoH measured by the SVI via regressions with surveillance and survival length, late-staging presentation, and treatment (surgery, radio-, chemotherapy) receipt. RESULTS: Increasing social vulnerability showed decreases in surveillance/survival; increased odds of advanced-presenting-stage (OR: 1.12, 95% CI: 1.07, 1.17), chemotherapy receipt (OR: 1.13, 95% CI: 1.03, 1.23); decreased odds of primary surgery (0.89, 0.84, 0.94), radiotherapy (0.91, 0.85, 0.97, p = 0.003) for SGCs. Trends were differentially correlated with SES, ML, HH, and HT-vulnerabilities. CONCLUSIONS: Through quantifying SDoH-derived SGC-disparities, the SVI can guide targeted initiatives against SDoH that elicit the most detrimental associations for specific sociodemographics.

Imaging of salivary gland cancers derived from a sublingual gland herniated into the submandibular space: a report of three cases.

Sublingual gland herniation into the submandibular space through a mylohyoid muscle defect is a common anatomical variation; however, salivary gland cancers that arise from a herniated sublingual gland have not been described yet. Here, we report three patients with salivary gland cancers originating from a herniated sublingual gland. All tumors were detected as palpable submandibular masses, located anterior to the submandibular gland, medial to the mandible, and lateral to the mylohyoid muscle, with contact with the sublingual gland through a mylohyoid muscle defect. Intraoperative findings confirmed that the masses were derived from herniated sublingual glands. Pathological examination showed one case of mucoepidermoid carcinoma and two cases of adenoid cystic carcinoma. Imaging findings of the tumor location, in addition to the continuity with the sublingual gland through the mylohyoid muscle defect, are crucial for accurately diagnosing the tumor origin, which is essential for determining the appropriate clinical management.

Exploring Immunological Effects and Novel Immune Adjuvants in Immunotherapy for Salivary Gland Cancers.

Salivary gland cancer (SGC) is rare and comprises over 20 histological subtypes. Recently, clinical experience regarding immunotherapies for SGCs has been accumulating, yet their efficacy remains controversial. Understanding the tumor microenvironment (TME), including the expression of immune checkpoint molecules in SGC, is crucial to optimizing immunotherapy. In this review, we demonstrate that high-grade mucoepidermoid carcinoma and salivary duct carcinoma generally exhibit immune-hot TME with high immune cell infiltration, frequent genetic mutations, and robust immune checkpoint molecule expression. In contrast, adenoid cystic carcinomas exhibit an immune-cold TME. While the reported efficacy of immune checkpoint inhibitors (ICIs) for SGCs is generally poor, several studies showed promising clinical efficacy of ICIs, with an objective response rate ranging from 20.0-33.3%, indicating that ICIs might be beneficial for a specific population of SGC. Molecule-targeted therapies including anti-human epidermal growth factor receptor 2 and anti-androgen receptor therapies have shown promising clinical efficacy against SGC. Recent evidence indicates that these molecules could be targets for antigen-specific immunotherapies including chimeric antigen receptor-T therapy and cancer vaccines. This review discusses the current understanding and future directions of immunotherapies for SGCs, including ongoing clinical trials.

Survival Impact of Elective Neck Dissection and Adjuvant Radiation in N0 High-Grade Mucoepidermoid Carcinoma.

OBJECTIVE: We aim to evaluate the role of elective neck dissection (END) and adjuvant radiation on survival in N0 high-grade mucoepidermoid carcinoma (MEC). STUDY DESIGN: Retrospective cohort study. SETTING: National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. METHODS: All patients diagnosed with high-grade MEC with node-negative disease (N0) from 2004 to 2018 were included. Demographic, clinicopathologic, treatment, and outcomes were analyzed. Kaplan-Meier survival curves were used to evaluate 5-year disease-specific survival (DSS) and 5-year overall survival (OS). Multivariate Cox regression analysis was used to control for confounders. RESULTS: A total of 310 patients with high-grade MEC and N0 (clinical and pathologic) disease were identified. The parotid was the most common primary site (266, 86%). Of included patients, 133 (42.9%) were T3-T4 tumors and 212 (68%) received adjuvant radiation. END was performed on 223 (71.9%) of cases. END in T3-T4 high-grade MEC led to significant improvements in DSS (74.3% vs 34.0%, P < .01) and OS (55.2% vs 20.5%, P < .01) as compared to no END. Subanalysis shows that in patients who received neck dissections and were pathologic N0, adjuvant radiation had no impact on DSS (84.0% vs 72.1%, P = .45) and OS (52.1% vs 55.8%, P = .91). Benefits persisted when controlling for confounders using multivariate Cox proportional regression. CONCLUSION: Patients with T3-T4 high-grade MEC who underwent END and found to be pathologically node-negative (pN0) had significantly improved 5-year DSS and 5-year OS than patients who were cN0 and did not undergo END. Importantly, although 68% of patients received adjuvant radiation, we show no benefit of this treatment modality on outcomes in pN0 high-grade MEC.

The tumor microenvironment of benign and malignant salivary gland tumors.

BACKGROUND: Treatment of salivary gland tumors (SGTs) remains challenging. Little is known about the immune landscape of SGTs. We aimed to characterize the tumor microenvironment in benign and malignant SGTs. METHODS: Eleven benign and nine malignant tumors were collected from patients undergoing curative intent surgery. Specimens were analyzed using mass cytometry by time-of-flight. Immune cell populations were manually gated, and T cells were clustered using the FlowSOM algorithm. Population frequencies were compared between high-grade and low-grade malignancies, corrected for multiple hypothesis testing. RESULTS: There were trends towards increased CD4+ and CD8+ T cells among malignant tumors. High-grade malignancies exhibited trends towards higher frequencies of CD8+ PD-1+ CD39+ CD103+ exhausted T cells, CD4+ FoxP3+ TCF-1+ CD127- Tregs, and CD69+ CD25- CD4+ T cells compared to low-grade malignancies. CONCLUSION: SGTs exhibit significant immunologic diversity. High-grade malignancies tended to have greater infiltration of exhausted CD8+ T cells and Tregs, which may guide future studies for immunotherapy strategies.

Twelve years after: The french national network on rare head and neck tumours (REFCOR).

BACKGROUND: Rare cancers constitute less than 10% of head and neck cancers and lack sufficient evidence for standardized care. The French Rare Head and Neck Cancer Expert Network (REFCOR) as established a national database to collect data on these rare cancers. This study aims to describe patient and tumour characteristics in this database. METHODS: Prospective data collection was conducted across multiple centers. Survival analyses were performed using Kaplan Meier method and Log Rank test. Odds ratios were used for comparing proportions. RESULTS: A total of 7208 patients were included over a period of 10 years. The most frequent histologies were: Not Otherwise Specified (NOS) adenocarcinoma 13 %, adenoid cystic carcinoma 12 %, squamous cell carcinoma of rare locations 10 %, mucoepidermoid carcinoma 9 %, intestinal-type adenocarcinoma (8 %). Tumours were located in sinonasal area (38 %); salivary glands (32 %); oral cavity / oropharynx / nasopharynx (16 %); larynx / hypopharynx (3 %); ears (1 %); others (3 %). Tumours were predominantly classified as T4 (23 %), N0 (54 %), and M0 (62 %). Primary treatment approach involved tumour resection (78 %) and / or radiotherapy (63 %). Patients with salivary gland cancers exhibited better 5-year overall survival (OS) rates (p < 0.05), and lower recurrence rates compared to patients with sinonasal, laryngeal/ hypopharyngeal cancers. No significant differences were observed in the other comparisons. Acinar cell carcinoma demonstrated the best OS while mucous melanoma had the poorest prognosis. CONCLUSION: Melanoma, carcinoma NOS, and sinonasal undifferenciated carcinoma still have poor prognoses. Efforts are being made, including training and guidelines, to expand network coverage (REFCOR, EURACAN), improve data collection and contribute to personalized therapies.

Near-Infrared Photoimmunotherapy Using a Protein Mimetic for EGFR-Positive Salivary Gland Cancer.

Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer therapy based on a monoclonal antibody (mAb) conjugated to a photosensitizer (IR700Dye). The conjugate can be activated by near-infrared light irradiation, causing necrotic cell death with high selectivity. In this study, we investigated NIR-PIT using a small protein mimetic (6-7 kDa, Affibody) which has more rapid clearance and better tissue penetration than mAbs for epidermal growth factor receptor (EGFR)-positive salivary gland cancer (SGC). The level of EGFR expression was examined in vitro using immunocytochemistry and Western blotting. Cell viability was analyzed using the alamarBlue assay. In vivo, the volume of EGFR-positive tumors treated with NIR-PIT using the EGFR Affibody-IR700Dye conjugate was followed for 43 days. It was found that NIR-PIT using the EGFR Affibody-IR700Dye conjugate induced the selective destruction of EGFR-positive SGC cells and restricted the progression of EGFR-positive tumors. We expect that NIR-PIT using the EGFR Affibody-IR700Dye conjugate can efficiently treat EGFR-positive SGC and preserve normal salivary function.

A 22-year single institution review of 119 cases of salivary duct carcinoma.

Objective: Salivary duct carcinoma (SDC) is a rare and aggressive salivary gland malignancy. Herein, we present the largest single-institution review of SDC to date. Methods: This is a retrospective cohort study of all histologically confirmed cases of SDC seen at our institution from January 1, 2002, to August 1, 2022. Patient demographics, treatment, histological characteristics, tumor staging, and outcomes were extracted from the electronic medical record. Kaplan-Meier and Cox regression survival analyses were performed. Results: This study included 119 patients with a mean age of 66.2 years. Most primary tumors arose from the parotid gland (72.3%), and 23.5% were noted to be carcinoma ex-pleomorphic adenoma. 57.1% of patients presented with regional lymph node metastasis, whereas 23.5% presented with distant disease. Kaplan-Meier analysis demonstrated a 62.4% 5-year overall survival (OS) and a 69.0% 5-year disease-specific survival (DSS). Univariate analyses indicated that presence of regional lymph node disease (p<.001), distant metastasis (p<.001), perineural invasion (p = .027), and lymphovascular invasion (p = .018) were predictive of decreased OS and DSS. Trastuzumab administration was not associated with survival in HER-2-positive patients receiving chemotherapy. Multivariate analyses demonstrated that presence of nodal disease (HR 30.337, 95% CI 2.782-330.851, p = .005) and carcinoma ex pleomorphic adenoma (HR 5.54, 95% CI 1.024-29.933, p = .047) were associated with decreased OS. Conclusion: Our patients had more favorable survival rates compared to prior studies, which may be due to lower incidence of nodal disease. Factors associated with worse survival included nodal and distant metastases, perineural invasion, lymphovascular invasion, and tumor size. Level of Evidence: Level 3.

Systemic therapies for salivary gland carcinomas: an overview of published clinical trials

Background: There is no consensus about effective systemic therapy for salivary gland carcinomas (sgcs). Our aim was summarized the clinical trials assessing the systemic therapies (ST) on sgcs.Material and Methods: Electronic searches were carried out through MEDLINE/pubmed, EMBASE, Scopus, Web of Science, and the Cochrane Library databases, and gray literature. Results: Seventeen different drugs were evaluated, and the most frequent histological subtype was adenoid cysticcarcinoma (n=195, 45.5%). Stable disease, observed in 11 ST, achieved the highest rate in adenoid cystic carcinoma treated with sunitinib. The highest complete (11.1%) and partial response (30.5%) rates were seen in androgen receptor-positive tumors treated with leuprorelin acetate. Conclusions: Despite all the advances in this field, there is yet no effective evidence-based regimen of ST, with all the clinical trials identified showing low rates of complete and partial responses. Further, translational studies are urgently required to characterize molecular targets and effective ST. (AU)

Choice of Adjuvant Radiotherapy Facility in Major Salivary Gland Cancer.

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.