Salivary Duct Carcinoma Patients Research Articles

The extent of androgen receptor and HER2 expression allows for targeted therapy in most cases of salivary duct carcinoma: analysis of clinical and histopathological data in a tertiary care center.

The incidence of salivary duct carcinoma (SDC) seems to be underestimated due to inaccurate classification. Further, the frequency of SDC patients with targeted therapy options according to current guidelines is unclear. Therefore, this study aimed at (a) describing the proportion of SDC among salivary gland carcinoma (SGC) before and after reclassification of cases initially classified as adenocarcinoma, not otherwise specified (ANOS); and (b) quantifying the frequency of SDC patients with targeted therapy options. All patients with SDC or ANOS treated in a tertiary care center between 1996 and 2023 were identified. Histopathological diagnosis was verified for patients primarily diagnosed with SDC and reviewed for patients initially diagnosed with ANOS. Clinical data for SDC patients were retrieved from clinical charts. Immunohistochemical (IHC) androgen receptor (AR) and HER2 staining was performed. Among 46 SDC, 34 were primarily diagnosed as SDC and 12 had initially been classified as ANOS. The proportion of SDC among SGC was 12.1% and was rising when comparing the time periods 2000-2015 (7.1-11.5%) versus 2016-2023 (15.4-18.1%). Nuclear AR staining in > 70% of tumor cells was found in 56.8% and HER2 positivity (IHC 3 +) in 36.4% of cases. 70.5% of patients showed AR staining in > 70% of tumor cells and/or HER2 positivity and therefore at least one molecular target. 5-year overall and disease-free survival (DFS) were 62.8% and 41.0%. Multivariate Cox regression revealed positive resection margins (HR = 4.0, p = 0.03) as independent negative predictor for DFS. The results suggest a rising SDC incidence and show that the extent of the AR and HER2 expression allows for targeted therapy in most SDC cases.

Retrospective analysis of genetically matched therapies in salivary gland cancer entities using a real-world database in a tertiary salivary gland cancer expertise center.

6098 Background: Salivary gland cancer (SGC) is a rare cancer and includes twenty-two different entities. In the Radboudumc SGC expertise center, a real-word database was set up to uniformly collect data of SGC subtypes. More than 500 SGC patients have been enrolled and collection of data for 261 patients is currently completed. Here, we describe the retrospective analysis of genetic aberrations found in different SGC entities and the treatment of selected recurrent/metastatic (R/M) patients with genetically matched therapies (GMT). Methods: All SGC patients in the SGC registry of Radboudumc between 2017 and 2022 whose tumors underwent next generation sequencing (NGS) and/or gene fusion analysis within standard of care or clinical trial were included in this analysis. Both primary tumor specimen and metastatic tissue have been used for molecular analyses. GMT was given in basket trials or on basis of compassionate use for clinically relevant genetic aberrations that are considered actionable nowadays. Results: NGS and/or gene fusion analysis data was available for 162 out of 261 patients, and most frequently in salivary duct carcinoma (SDC) patients (82/162). The number of patients with genetic aberrations differed between SGC entities. In 112 patients at least one genetic aberration and/or gene fusion was detected regardless of whether the target was druggable. Ninety-three patients out of 112 patients had R/M disease. Both a gene fusion and one or more mutations were found in six patients (adenoid cystic carcinoma [AdCC], n = 3; SDC, n = 2; and secretary carcinoma [SC], n = 1;). Depending on the SGC subtype, in 14.3 – 100% of the R/M cases with genetic aberrations and/or gene fusions a GMT was started (SDC, 14/60; AdCC, 3/21; SC, 2/2; mucoepidermoid carcinoma, 2/4). The most given GMT among patients were monoclonal antibodies and tyrosine kinase inhibitors (TKI), respectively in nine and eleven patients, moreover immunotherapy was started in one patient. For example, eight SDC patients were treated with ERBB2 targeting agents (4/8 mutations; 4/8 copy number variants in ERBB2), showing a complete response in three patients. Additionally, one partial response and two stable diseases were observed, two patients were lost of follow-up. Two SC patients treated with a TKI based on the presence of the ETV6- NTRK gene fusion showed radiologically a partial response. Conclusions: In 69% of the SGC patients at least one genetic aberration and/or gene fusion was found, and in 23% of the R/M cases GMT was administered. Response differs between entities and GMT; a complete response was achieved after initiation of GMT in several patients. These data justify the use of NGS and gene fusion analysis in all salivary gland cancer entities, notably in subtypes lacking standard systemic therapies as this could offer other therapeutic options.

Her2 expression can predict the survival of patients with salivary duct carcinoma

Salivary duct carcinoma (SDC) is a high-grade malignant tumor that mainly develops in the salivary glands, and SDC patients have a 5-year survival rate of less than 50%. Thirteen SDC patients (11 male and 2 female, average age 67.2 years) with primary salivary gland carcinoma who received primary treatment in our department from 2005 to 2016. Although markers such as androgen receptors and gross cystic disease fluid protein-15 are effective in diagnosing SDC, there are no effective tumor-specific markers for prognosis prediction. Therefore, we investigated the expressions of human epidermal growth factor receptor 2 (Her2), Ki-67, EGFR, p16, P53 and PD-L1, and examined their prognostic effect. Multivariate analysis showed that high Her2 expression was an exacerbating prognostic factor. In the future, the use of molecular-targeted drugs and immune checkpoint inhibitors for salivary gland malignancies may become more frequent. Her2 expression could be used as a predictor of prognosis.

Prognostic models for estimating survival of salivary duct carcinoma: a population-based study.

In a large salivary duct carcinoma (SDC) cohort, we aimed to investigate the clinical factors influencing their survival outcomes and to further establish prognostic models. Data of patients with SDC were extracted from the Surveillance, Epidemiology, and End Results database (1975-2019). A retrospective analysis was conducted to explore the prognostic factors on overall survival (OS) and disease-specific survival (DSS), and corresponding nomograms were established. A steady upward trend in the incidence of SDC was observed over the past four decades. Totally, 399 patients (280 in the training set and 199 in the testing set) were enrolled. Advanced T stage, lymph node metastasis, distant metastasis, and surgery were associated with favorable OS and DSS. Besides, age > 80years exhibited worse OS. The selected variables above were used to construct nomograms and online web calculators that could accurately predict patient survival. In addition, risk stratification systems were generated to identify low- and high-risk patients. As the risk level increased, the risk of both patient mortality and disease-specific mortality increased. The SDC incidence was low, but steadily increasing. The proposed prognostic models provided a robust and efficient approach to predict survival and risk stratification in SDC patients.

Clinical value of adjuvant therapy on the prognosis of ductal carcinoma of the major salivary gland: a large-scale cohort study.

To explore the clinical characteristics, prognostic factors, and value of adjuvant therapy for major salivary duct carcinoma (SDC). Data of SDC patients who received surgery was obtained from Surveillance, Epidemiology, and End Results (SEER) database (2004-2016). Kaplan-Meier and Cox regression analyses were performed to assess prognostic factors. Propensity score matching (PSM) was done to evaluate the clinical value of adjuvant therapy. A total of 287 patients were enrolled. The 5-year overall survival (OS) and disease-specific survival (DSS) rates were 53.8% and 70.8%, respectively. In the univariate analysis, tumor size, T, N, TNM staging, SEER combined staging, number of regional lymph nodes examined, and number of positive lymph nodes were associated with OS and DSS. Age and primary surgical methods were also related to OS. Among patients with negative lymph nodes, patients with tumor size > 4cm had significantly worse prognosis (P = 0.009). Multivariate analysis showed that age > 75years, T3-4, and positive lymph nodes were independent risk factors for SDC. After PSM, the prognostic factors were age, tumor site, and T and N stage. Postoperative radiotherapy could improve OS in patients with tumor size > 4cm (P = 0.049). Advanced age, submandibular gland lesions, T3-4stage, and lymph node involvement were independent prognostic factors for SDC. In patients with tumors > 4cm, adjuvant radiotherapy improved the OS of SDC patients.

The Role of the EZH2 and H3K27me3 Expression as a Predictor of Clinical Outcomes in Salivary Duct Carcinoma Patients: A Large-Series Study With Emphasis on the Relevance to the Combined Androgen Blockade and HER2-Targeted Therapy.

ObjectiveSalivary duct carcinoma (SDC) is a highly aggressive and uncommon tumor arising not only de novo but also in pleomorphic adenoma. Androgen receptor (AR)- and HER2-targeted therapy have recently been introduced for SDC as promising treatment options; however, no predictive biomarkers have yet been established. EZH2 and H3K27me3 are closely linked to the development and progression of various cancers, and EZH2 is also expected to be a desirable therapeutic target. We therefore explored the clinicopathological and prognostic implications of EZH2 and H3K27me3 in a large cohort of SDC patients, focusing on their impact on the therapeutic efficacy of AR- or HER2-targeted therapy.Materials and MethodsThe EZH2 and H3K27me3 immunohistochemical expression and EZH2 Y646 gain-of-function mutation status were examined in 226 SDCs, and the relationship with the clinicopathological factors as well as clinical outcomes were evaluated within the three groups depending on the treatment: AR-targeted (combined androgen blockade with leuprorelin acetate and bicalutamide; 89 cases), HER2-targeted (trastuzumab and docetaxel; 42 cases), and conventional therapy (112 cases).ResultsEZH2 and H3K27me3 were variably immunoreactive in most SDCs. A positive correlation was found between the expression of EZH2 and H3K27me3. The EZH2 expression in the SDC component was significantly higher than that in the pre-existing pleomorphic adenoma component. EZH2 Y646 was not identified in any cases. EZH2-high cases more frequently had an advanced clinical stage and aggressive histological features than EZH2-low cases. An EZH2-high status in patients treated with AR-targeted therapy was associated with a significantly shorter progression-free and overall survival as well as a lower objective response rate and clinical benefit rate. In addition, a H3K27me3-high status in patients treated with AR-targeted therapy was related to a shorter overall survival. Conversely, there was no association between the EZH2 and H3K27me3 expression and the clinical outcomes in the conventional or HER2-targeted therapy groups.ConclusionsA high expression of EZH2 and H3K27me3 in SDC might be a predictor of a poor efficacy of AR-targeted therapy. Our data provide new insights into the role of EZH2 and H3K27me3 in therapeutic strategies for SDC.

Treatment Efficacy of PD-1 Inhibitor Therapy in Patients With Recurrent and/or Metastatic Salivary Gland Carcinoma.

The efficacy of programmed cell death 1 (PD-1) inhibitor therapy for patients with recurrent and/or metastatic salivary gland carcinoma (R/M SGC) remains unclear. We retrospectively analyzed 36 patients with R/M SGC treated with PD-1 inhibitor. The expression of programmed cell death ligand 1 (PD-L1) and mismatch repair (MMR) proteins was also analyzed. The objective response rate (ORR) was 11.1%. The histopathological subtypes of patients who achieved complete response or partial response were salivary duct carcinoma (SDC) in three patients and poorly differentiated carcinoma in one patient, all of whom showed a positive PD-L1 expression. The expression of MMR proteins was not associated with the efficacy of PD-1 inhibitors. Although the efficacy of PD-1 inhibitor therapy in R/M SGC is limited, certain patients may respond and achieve long-term disease control. There is a potential therapeutic effect in SDC patients with positive PD-L1 expression.

Survival benefit of HER2-targeted or androgen deprivation therapy in salivary duct carcinoma.

Background:The efficacy and safety of human epidermal growth factor receptor 2 (HER2)-targeted therapy and androgen deprivation therapy (ADT) for locally advanced or recurrent or metastatic (LA/RM) salivary duct carcinoma (SDC) have been reported in prospective studies. However, the survival benefit of these therapies to conventional therapy remains controversial, and whether HER2-targeted therapy or ADT should be chosen in HER2- and androgen receptor (AR)-positive SDC patients remains unknown.Methods:Overall, 323 LA/RM SDC patients treated at seven institutions between August 1992 and June 2020 were retrospectively enrolled. The primary aim was to analyze the effect of HER2-targeted therapy and ADT on overall survival from the diagnosis of LA/RM disease to death from any cause (OS1). The secondary indicators included the overall response rate (ORR), clinical benefit rate (CBR), overall survival from therapy initiation for LA/RM disease (OS2), progression-free survival (PFS), time to second progression (PFS2), duration of response (DoR), and duration of clinical benefit (DoCB) of HER2-targeted therapy or ADT as first-line therapy for HER2-positive/AR-positive SDC.Results:Patients treated with HER2-targeted therapy or ADT had longer OS1 than those treated without these therapies (Median OS1: historical control, 21.6 months; HER2-targeted therapy, 50.6 months; ADT, 32.8 months; HER2-targeted therapy followed by ADT, 42.4 months; and ADT followed by HER2-targeted therapy, 45.2 months, p < 0.001). Among HER2-positive/AR-positive SDC patients, although HER2-targeted therapy had better ORR, CBR, and PFS than those of ADT as first-line therapy, we found no significant differences between HER2-targeted therapy and ADT regarding OS2, PFS2, DoR, and DoCB.Conclusion:Patients treated with HER2-targeted therapy and ADT showed longer survival in LA/RM SDC. HER2-targeted therapy can be recommended prior to ADT for HER2-positive/AR-positive SDC. It is warranted to establish a biomarker that could predict the efficacy of clinical benefit or better response in ADT.

911P Case series of docetaxel, trastuzumab, and pertuzumab (DTP) and subsequent ado-trastuzumab emtansine (T-DM1) for recurrent or metastatic (R/M) HER2-positive salivary duct carcinoma (SDC)

SDC is an aggressive subtype of salivary gland cancer. In R/M disease, androgen deprivation therapy (ADT) resulted in response rates (RR) of 18-53% in androgen receptor-positive SDC. SDCs are HER2-positive in 29-46% of cases and have shown RR of 70% on docetaxel and trastuzumab. Here, we present the results of HER2-positive SDC patients treated with DTP and subsequent T-DM1.

Predictive and Prognostic Biomarker Identification in a Large Cohort of Androgen Receptor-Positive Salivary Duct Carcinoma Patients Scheduled for Combined Androgen Blockade.

Simple SummaryAndrogen receptor signaling seems pivotal in aggressive salivary duct carcinoma. However, androgen deprivation therapy (ADT) frequently fails, emphasizing the need for biomarkers to predict treatment response. Here, the activities of several possible tumor-driving pathways were quantified and related to clinical outcome in a large cohort of SDC patients. Our results indicated that AR pathway activity and SRD5A1 expression levels can be used to predict response to ADT, which could prevent overtreatment in clinical practice.Patients suffering from recurrent or metastatic (R/M) salivary duct carcinoma (SDC) are often treated with combined androgen blockade (CAB). However, CAB frequently fails, resulting in a worse prognosis. Therefore, biomarkers that can predict treatment failure are urgently needed. mRNA from 76 R/M androgen receptor (AR)-positive SDC patients treated with leuprorelin acetate combined with bicalutamide was extracted from pre-treatment tumor specimens. AR, Notch, MAPK, TGFβ, estrogen receptor (ER), Hedgehog (HH), and PI3K signaling pathway activity scores (PAS) were determined based on the expression levels of target genes. Additionally, 5-alpha reductase type 1 (SRD5A1) expression was determined. These markers were related to clinical benefit (complete/partial response or stable disease ≥6 months) and progression-free and overall survival (PFS/OS). SRD5A1 expression had the highest general predictive value for clinical benefit and positive predictive value (PPV: 85.7%). AR PAS had the highest negative predictive value (NPV: 93.3%). The fitting of a multivariable model led to the identification of SRD5A1, TGFβ, and Notch PAS as the most predictive combination. High AR, high Notch, high ER, low HH PAS, and high SRD5A1 expression were also of prognostic importance regarding PFS and SRD5A1 expression levels for OS. AR, Notch PAS, and SRD5A1 expression have the potential to predict the clinical benefit of CAB treatment in SDC patients. SRD5A1 expression can identify patients that will and AR PAS patients that will not experience clinical benefit (85.7% and 93.3% for PPV and NPV, respectively). The predictive potential of SRD5A1 expression forms a rational basis for including SRD5A1-inhibitors in SDC patients’ treatment.

Predictive and prognostic biomarker identification in a large cohort of androgen receptor-positive salivary duct carcinoma patients scheduled for combined androgen blockade.

6071 Background: Patients suffering from recurrent or metastatic (R/M) salivary duct carcinoma (SDC) are often treated with combined androgen blockade (CAB). This treatment however frequently fails (response rates: 18-53%), resulting in a worse prognosis. Therefore, biomarkers that have prognostic value and can predict treatment response are urgently needed. Methods: mRNA from 77 R/M androgen receptor (AR) positive SDC patients treated with leuprorelin acetate combined with bicalutamide was extracted from pre-treatment tumor specimens. AR, Notch, Mitogen-Activated Protein Kinase (MAPK), Transforming Growth Factor beta (TGFβ), Estrogen Receptor (ER), Hedgehog (HH) and the Phosphoinositide 3-Kinase (PI3K) signaling pathway activities were calculated based on expression levels of relevant target genes. Besides this, 5-alpha reductase type 1 ( SRD5A1) expression and Human Epidermal growth factor Receptor 2 (HER2) status were determined. Clinical benefit was defined as complete or partial response or stable disease ≥6 months. Results: Of the 7 signaling pathways, AR pathway activity was the best predictor of clinical benefit (AUC 0.67, 95%-CI 0.54-0.80). At a threshold of 47.8, 21% of the patients tested negative, with a negative predictive value of 93%. SRD5A1 expression outperformed the signaling pathways regarding predictive value (AUC 0.78, 95%-CI 0.67-0.88). Fitting of a multivariable model led to the identification of SRD5A1, Notch and TGFβ as most predictive combination (AUC 0.82, 95%-CI 0.72-0.91). AR, Notch, HH and SRD5A1 were also of prognostic importance regarding progression free survival and SRD5A1 expression levels also for overall survival (median of 175.0 weeks for high versus 96.7 weeks for low expression). Conclusions: Our study revealed predictive and/or prognostic value of AR, HH, Notch and TGFβ signaling activities and SRD5A1 expression in SDC patients treated with CAB. AR pathway activity can be used for identifying non-responders. Further clinical validation is required before implementation of these biomarkers in clinical practice. The observed role of SRD5A1 expression in CAB response forms a rational basis for including SRD5A1-inhibitors in the treatment of SDC patients.[Table: see text]

A population-based competing risk survival analysis of patients with salivary duct carcinoma.

BackgroundSalivary duct carcinoma (SDC) is a rare malignancy with high risk of local recurrence and distant metastases of the salivary gland. This study was designed to summarize the clinical and pathological features and to further evaluate them as potential prognostic factors for SDC in the salivary gland.MethodsClinical data of 266 patients diagnosed with SDC between 2004 and 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. The prognostic factors affecting overall survival (OS) and cancer-specific survival (CSS) were determined by Kaplan-Meier analyses and Cox proportional hazards model. The nomogram was established to predict OS and CSS for SDC. The predictive accuracy of the nomograms was measured by concordance index (C-index).ResultsThe 3- and 5-year OS of SDC patients were 67.41% and 47.86%, while the 3- and 5-year CSS were 84.6% and 60.7%, respectively. The primary site, T stage and M stage were identified as independent prognostic factors for OS by the multivariate analysis, whereas N stage, M stage, the presence of multiple primary carcinomas and the treatment modalities were identified as independent prognostic factors for CSS. The C-index values of the prognostic nomogram based the risk factors affecting SDC OS and CSS were 0.703 (0.646–0.760) and 0.771 (0.691–0.851), respectively.ConclusionsSDC is an aggressive malignancy with a high proportion of advanced stage and lymph node metastases. Patients with increasing age, submandibular gland malignancy, advanced T stage, advanced N stage, advanced M stage, high lymph node ratio (LNR) and the presence of multiple primary carcinomas tend to have unfavorable outcomes. Radiotherapy or chemotherapy improve CSS remarkably. These factors will aid in effective therapeutic treatment modalities for SDC.

Prediction of clinical benefit from androgen deprivation therapy in salivary duct carcinoma patients.

Androgen deprivation therapy (ADT) is first‐line palliative treatment in androgen receptor‐positive (AR+) salivary duct carcinoma (SDC), and response rates are 17.6–50.0%. We investigated potential primary ADT resistance mechanisms for their predictive value of clinical benefit from ADT in a cohort of recurrent/metastatic SDC patients receiving palliative ADT (n = 30). We examined mRNA expression of androgen receptor (AR), AR splice variant‐7, intratumoral androgen synthesis enzyme‐encoding genes AKR1C3, CYP17A1, SRD5A1 and SRD5A2, AR protein expression, ERBB2 (HER2) gene amplification and DNA mutations in driver genes. Furthermore, functional AR pathway activity was determined using a previously reported Bayesian model which infers pathway activity from AR target gene expression levels. SRD5A1 expression levels and AR pathway activity scores were significantly higher in patients with clinical benefit from ADT compared to those without benefit. Survival analysis showed a trend toward a longer median progression‐free survival for patients with high SRD5A1 expression levels and high AR pathway activity scores. The AR pathway activity analysis, and not SRD5A1 expression, also showed a trend toward better disease‐free survival in an independent cohort of locally advanced SDC patients receiving adjuvant ADT (n = 14) after surgical tumor resection, and in most cases a neck dissection (13/14 patients) and postoperative radiotherapy (13/14 patients). In conclusion, we are the first to describe that AR pathway activity may predict clinical benefit from ADT in SDC patients, but validation in a prospective study is needed.

Prognostic Implication of Histopathologic Indicators in Salivary Duct Carcinoma: Proposal of a Novel Histologic Risk Stratification Model.

Salivary duct carcinoma (SDC) is a rare, aggressive malignancy that histologically resembles high-grade mammary duct carcinoma. Because of the rarity of this entity, data verifying the association between histologic features and patient survival are limited. We conducted a comprehensive histologic review of 151 SDC cases and performed an analysis of the association between various histomorphologic parameters and the clinical outcome with the aim of developing a histologic risk stratification model that predicts the prognosis of SDC patients. A multivariate analysis revealed that prominent nuclear pleomorphism (overall survival [OS]: P=0.013; progression-free survival [PFS]: P=0.019), ≥30 mitoses/10 HPF (PFS: P=0.013), high tumor budding (OS: P=0.011; PFS: P<0.001), and high poorly differentiated clusters (OS: P<0.001; PFS: P<0.001) were independent prognostic factors. Patients with vascular invasion demonstrated a marginally significant association with shorter PFS (P=0.064) in a multivariate analysis. We proposed a 3-tier histologic risk stratification model based on the total number of positive factors among 4 prognostically relevant parameters (prominent nuclear pleomorphism, ≥30 mitoses/10 HPF, vascular invasion, and high poorly differentiated clusters). The OS and PFS of patients with low-risk (0 to 1 point) (23% of cases), intermediate-risk (2 to 3 points) (54% of cases), and high-risk (4 points) (23% of cases) tumors progressively deteriorated in this order (hazard ratio, 2.13 and 2.28, and 4.99 and 4.50, respectively; Ptrend<0.001). Our histologic risk stratification model could effectively predict patient survival and may be a useful aid to guide clinical decision-making in relation to the management of patients with SDC.

1342P - 68Ga-PSMA-PET/CT imaging for locally advanced, recurrent and metastatic adenoid cystic carcinoma and salivary duct carcinoma

Background: Salivary gland cancer (SGC) is a rare cancer with few treatment options. Adenoid cystic carcinoma (ACC) and salivary duct carcinoma (SDC) are major subtypes of SGC which often show immunohistochemical expression of prostate-specific membrane antigen (PSMA). In prostate cancer, PSMA ligands labeled with radioisotopes such as 68Ga or 177Lu, are used for imaging or therapy. The aim of this study was to evaluate 68Ga-PSMA ligand uptake in patients with locally recurrent and/or metastatic ACC and SDC and to establish the diagnostic value of 68Ga-PSMA-PET/CT imaging compared to full-dose CT imaging. Methods:68Ga-PSMA-HBED-CC PET/CT scans were performed in 14 ACC patients and 10 SDC patients including a full-dose CT scan of the neck, chest and abdomen. 68Ga-PSMA ligand uptake was evaluated in local recurrences and metastatic lesions. Detected lesions were compared to CT results. Maximum standardized uptake values (SUVmax) were determined. The study protocol was approved by the local medical ethical committee and a written informed consent was obtained from all patients. Results: Moderate to intense PSMA ligand uptake was observed in local recurrences and distant metastases in all ACC patients and 40% of SDC patients. In addition, PSMA-PET imaging detected additional bone metastases in 2 ACC patients and additional lymph node metastases in 1 ACC patient which were not detected on a full-dose CT scan. In 1 ACC patient a local recurrence of a vulvar ACC was suspected on CT but PSMA-PET imaging was negative, which turned out to be scar tissue, eventually. Conclusions: PSMA-PET imaging showed moderate to intense ligand uptake in local recurrences and distant metastases of all ACC patients and 40% of SDC patients. Based on the high uptake, these patients may be promising candidates for 177Lu-PSMA radioligand therapy in future. Moreover, PSMA-PET imaging has added diagnostic value compared to full-dose CT imaging. Clinical trial identification: NCT03319641. Legal entity responsible for the study: Radboud university medical center, Nijmegen, the Netherlands. Funding: Adenoid Cystic Carcinoma Research Foundation (ACCRF) and the Dutch Salivary Gland Cancer Patient Platform. Disclosure: All authors have declared no conflicts of interest.

Expression pattern of androgen receptor and AR-V7 in androgen-deprivation therapy–naïve salivary duct carcinomas

Androgen-deprivation therapy has been used to treat salivary duct carcinoma (SDC). The androgen receptor splice variant-7 (AR-V7) has been detected in castration-resistant prostate cancer and implicated in resistance to androgen receptor (AR)-targeted therapies. Given the potential role of AR/AR-V7 in SDC treatment, this study focuses on AR/AR-V7 expression in SDC specimens collected before androgen-deprivation therapy. RNA in situ hybridization (ISH) and immunohistochemistry (IHC) to detect total AR and AR-V7 were performed on formalin-fixed, paraffin-embedded SDC specimens from 23 patients. Full-length AR and AR-V7 transcripts were quantified in a subset of tumors by reverse-transcription polymerase chain reaction. Twenty SDCs were positive for total AR by ISH and IHC. Among AR-positive SDCs, 70% (14/20) were positive for AR-V7 messenger RNA by ISH, whereas 15% (3/20) were positive for AR-V7 protein by IHC. The 3 SDCs that expressed the highest levels of AR-V7 were all from female patients; one of them expressed a significant amount of AR-V7 and barely detectable full-length AR transcripts by reverse-transcription polymerase chain reaction. IHC expression of Forkhead box protein A1, prostate-specific antigen, prostatic acid phosphatase, and NKX3.1 was observed in some SDCs regardless of patient sex. Five SDCs demonstrated strong human epidermal growth factor receptor 2 expression. We conclude that treatment-naïve SDCs may express AR-V7 at levels comparable to or even exceeding the levels detected in castration-resistant prostate cancer. Our data support the feasibility to incorporate AR-V7 assessment via ISH and/or IHC in the ongoing clinical trials evaluating the therapeutic benefit of AR-targeted therapies in SDC patients.

Clinicopathological Behavior and Treatment-related Outcome of Rare Salivary Duct Carcinoma: The Shaukat Khanum Memorial Cancer Hospital Experience

BackgroundSalivary gland tumors are rare salivary gland malignancies with resemblance to ductal breast carcinoma. We have described clinicopathological behavior and treatment outcomes of this rare malignancy.MethodsSalivary duct carcinoma patients treated from 2010 to 2015 were retrospectively analyzed for clinicopathological characteristics and treatment-related outcomes of the disease.ResultsA total of 12 patients with salivary duct carcinoma were included in the study. All were males with mean age of 52.58 ± 13.43. Parotid gland was the most commonly involved major salivary gland while buccal mucosa and anterior tongue were most common oral cavity sub-sites involving minor salivary glands. The disease-free survival was 75% at 10 months and 25% at 20 months. The mean follow-up time was 12 months. There were three local recurrences and one distant metastasis.ConclusionSalivary duct carcinoma is a locally aggressive tumor with tendency for local recurrence and distant metastasis. Adverse features such as perineural invasion, extra-capsular spread and advanced nodal disease may worsen prognosis.

A clinicopathological study and prognostic factor analysis of 177 salivary duct carcinoma patients from The Netherlands.

Salivary duct carcinoma (SDC) is a subtype of salivary gland cancer with a dismal prognosis and a need for better prognostication and novel treatments. The aim of this national cohort study was to investigate clinical outcome, prognostic factors, androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) expression. SDC patients diagnosed between 1990 and 2014 were identified by the Nationwide Network and Registry of Histo‐ and Cytopathology in the Netherlands (PALGA). Subsequently, medical records were evaluated and pathological diagnoses reviewed. Data were analyzed for overall survival (OS), disease‐free survival (DFS), distant metastasis‐free survival (DMFS) and prognostic factors. AR was evaluated by immunohistochemistry (IHC), HER2 by IHC and fluorescent in‐situ hybridization. A total of 177 patients were included. The median age was 65 years, 75% were male. At diagnosis, 68% presented with lymph node metastases and 6% with distant metastases. Median OS, DFS and DMFS were 51, 23 and 26 months, respectively. In patients presenting without distant metastases, the absolute number of positive lymph nodes was associated with poor OS and DMFS in a multivariable analysis. AR and HER2 were positive in 161/168 (96%) and 44/153 (29%) tumors, respectively, and were not prognostic factors. SDC has a dismal prognosis with primary lymph node involvement in the majority of patients. The absolute number of lymph node metastases was found to be the only prognostic factor for DMFS and OS. AR expression and—to a lesser extent—HER2 expression hold promise for systemic treatment in the metastatic and eventually adjuvant setting.

Cervical Lymph Node Metastatic Status and Adjuvant Therapy Predict the Prognosis of Salivary Duct Carcinoma

Salivary duct carcinoma (SDC) is an aggressive malignancy that is not yet fully understood. We designed the present retrospective study to investigate the factors affecting the prognosis of SDC and the effects of adjuvant therapies on the clinical outcomes of patients. Patients with SDC treated surgically from 2006 to 2016 were enrolled in the present retrospective cohort study. The demographic data, clinical pathologic characteristics, and follow-up results were recorded. The prognostic indicators of overall survival (OS), locoregional failure-free survival (LRFFS), and distant metastasis-free survival (DMFS) were analyzed using the Kaplan-Meier method and the Cox proportional hazard model. The study sample included 66 patients, most of whom were male (81.8%). The 5-year OS, LRFFS, and DMFS for all patients was 52.5%, 63.9%, and 51.3%, respectively. Univariate analysis showed that stage N2-N3, lymph node involvement of levels IV and V, 8 or more positive lymph nodes, and extranodal extension were all negative prognostic indicators for OS. The only significant indicator on multivariate analysis was the number of positive lymph nodes. Multivariate analysis revealed that extracapsular invasion and no adjuvant radiotherapy were risk factors for LRFFS. In contrast, lesions involving both glands and 8 or more positive lymph nodes were prognostic factors for DMFS. Further subgroup analysis showed that radiotherapy was only useful for patients with locally advanced lesions for local control. Cervical lymph node metastatic status is an important factor in predicting the prognosis of SDC patients. Adjuvant radiotherapy is useful for local control, especially for patients with stage T4 disease but does not benefit OS and DMFS.

223Ra Dichloride Bone-Targeted Therapy in a Case of Metastatic Salivary Duct Carcinoma

Salivary duct carcinoma (SDC) is a rare malignancy, frequently overexpressing androgen receptor (AR). Therefore, similar to AR-positive prostate cancer (PCa), AR-positive SDC patients benefit from androgen deprivation therapy and, after progression on ADT, might take advantage of Ra dichloride, a radiopharmaceutical approved for the treatment of castration-resistant PCa with symptomatic bone disease. We report the case of a 75-year-old man with castration-resistant SDC and osteoblastic bone metastases who, after Ra treatment, achieved adequate control of bone pain and bone lesion reduction with minor side effects. Evaluation of this strategy in other patients with similar characteristics is warranted.